OMA1 is a mitochondrial membrane zinc metalloprotease involved in stress-responsive protein processing and quality control. Its conserved catalytic architecture supports cleavage of mitochondrial substrates; mammalian OMA1 controls OPA1 processing and signals mitochondrial stress through DELE1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002024 diet induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Thermogenic adaptation is a downstream mammalian phenotype of mitochondrial quality control rather than the defining protease function. Reason: Thermogenic adaptation is a downstream mammalian phenotype of mitochondrial quality control rather than the defining protease function. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0002024 diet induced thermogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Thermogenic adaptation is a downstream mammalian phenotype of mitochondrial quality control rather than the defining protease function. Reason: Thermogenic adaptation is a downstream mammalian phenotype of mitochondrial quality control rather than the defining protease function. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:25275009 Activation of mitochondrial protease OMA1 by Bax and Bak pro... | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:32132706 A pathway coordinated by DELE1 relays mitochondrial stress t... | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | IMP PMID:20038677 Inducible proteolytic inactivation of OPA1 mediated by the O... | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0004222 metalloendopeptidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Reason: Human-cell OPA1 cleavage experiments establish OMA1 as a zinc-dependent mitochondrial metalloprotease. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MODIFY | Summary: The inner membrane is the more precise established mitochondrial location. Reason: The inner membrane is the more precise established mitochondrial location. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | MODIFY | Summary: The inner membrane is the more precise established mitochondrial location. Reason: The inner membrane is the more precise established mitochondrial location. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-8867344 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9840408 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9840564 | ACCEPT | Summary: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Reason: OMA1 is an inner-mitochondrial-membrane protease; the characterized human protein has the catalytic membrane-protease architecture. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:32132706 A pathway coordinated by DELE1 relays mitochondrial stress t... | ACCEPT | Summary: The catalytic region operates on the intermembrane-space side of the inner membrane; this is compatible with its membrane residence. Reason: The catalytic region operates on the intermembrane-space side of the inner membrane; this is compatible with its membrane residence. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: The catalytic region operates on the intermembrane-space side of the inner membrane; this is compatible with its membrane residence. Reason: The catalytic region operates on the intermembrane-space side of the inner membrane; this is compatible with its membrane residence. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0006006 glucose metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glucose metabolism can be affected through mitochondrial quality control and stress adaptation; OMA1 is not a glucose-metabolizing enzyme. Reason: Glucose metabolism can be affected through mitochondrial quality control and stress adaptation; OMA1 is not a glucose-metabolizing enzyme. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006006 glucose metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Glucose metabolism can be affected through mitochondrial quality control and stress adaptation; OMA1 is not a glucose-metabolizing enzyme. Reason: Glucose metabolism can be affected through mitochondrial quality control and stress adaptation; OMA1 is not a glucose-metabolizing enzyme. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: OMA1 catalyzes cleavage of protein substrates including OPA1. Reason: OMA1 catalyzes cleavage of protein substrates including OPA1. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006515 protein quality control | IBA GO_REF:0000033 | ACCEPT | Summary: Stress-induced substrate cleavage contributes to mitochondrial protein and organelle quality control. Reason: Stress-induced substrate cleavage contributes to mitochondrial protein and organelle quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006515 protein quality control | IMP PMID:20038677 Inducible proteolytic inactivation of OPA1 mediated by the O... | ACCEPT | Summary: Stress-induced substrate cleavage contributes to mitochondrial protein and organelle quality control. Reason: Stress-induced substrate cleavage contributes to mitochondrial protein and organelle quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lipid metabolism is a downstream physiological context of mitochondrial maintenance rather than a lipid-catalytic activity of OMA1. Reason: Lipid metabolism is a downstream physiological context of mitochondrial maintenance rather than a lipid-catalytic activity of OMA1. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0006629 lipid metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lipid metabolism is a downstream physiological context of mitochondrial maintenance rather than a lipid-catalytic activity of OMA1. Reason: Lipid metabolism is a downstream physiological context of mitochondrial maintenance rather than a lipid-catalytic activity of OMA1. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0010637 negative regulation of mitochondrial fusion | IEA GO_REF:0000107 | ACCEPT | Summary: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Reason: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0010637 negative regulation of mitochondrial fusion | IMP PMID:20038677 Inducible proteolytic inactivation of OPA1 mediated by the O... | ACCEPT | Summary: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Reason: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0010637 negative regulation of mitochondrial fusion | ISS GO_REF:0000024 | ACCEPT | Summary: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Reason: Stress-induced OPA1 cleavage reduces fusion competence, as demonstrated by OMA1 knockdown in mammalian cells. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0016540 protein autoprocessing | IEA GO_REF:0000107 | UNDECIDED | Summary: OMA1 processing is established, but distinguishing self-cleavage from cleavage by another protease requires the particular mechanistic experiment behind this transfer. Reason: OMA1 processing is established, but distinguishing self-cleavage from cleavage by another protease requires the particular mechanistic experiment behind this transfer. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0016540 protein autoprocessing | ISS GO_REF:0000024 | UNDECIDED | Summary: OMA1 processing is established, but distinguishing self-cleavage from cleavage by another protease requires the particular mechanistic experiment behind this transfer. Reason: OMA1 processing is established, but distinguishing self-cleavage from cleavage by another protease requires the particular mechanistic experiment behind this transfer. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0031638 zymogen activation | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific activation substrate and cleavage event underlying this annotation require examination; generic stress-dependent protease activation does not identify a zymogen-activation reaction. Reason: The specific activation substrate and cleavage event underlying this annotation require examination; generic stress-dependent protease activation does not identify a zymogen-activation reaction. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0031638 zymogen activation | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific activation substrate and cleavage event underlying this annotation require examination; generic stress-dependent protease activation does not identify a zymogen-activation reaction. Reason: The specific activation substrate and cleavage event underlying this annotation require examination; generic stress-dependent protease activation does not identify a zymogen-activation reaction. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0031966 mitochondrial membrane | IDA PMID:20038677 Inducible proteolytic inactivation of OPA1 mediated by the O... | MODIFY | Summary: Mitochondrial inner membrane specifies the conserved location. Reason: Mitochondrial inner membrane specifies the conserved location. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. |
| GO:0033108 mitochondrial respiratory chain complex assembly | IEA GO_REF:0000107 | UNDECIDED | Summary: OMA1 can influence respiratory-complex stability, but direct participation in assembly requires substrate- and complex-specific evidence beyond general mitochondrial quality control. Reason: OMA1 can influence respiratory-complex stability, but direct participation in assembly requires substrate- and complex-specific evidence beyond general mitochondrial quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0033108 mitochondrial respiratory chain complex assembly | ISS GO_REF:0000024 | UNDECIDED | Summary: OMA1 can influence respiratory-complex stability, but direct participation in assembly requires substrate- and complex-specific evidence beyond general mitochondrial quality control. Reason: OMA1 can influence respiratory-complex stability, but direct participation in assembly requires substrate- and complex-specific evidence beyond general mitochondrial quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0033554 cellular response to stress | IDA PMID:32132706 A pathway coordinated by DELE1 relays mitochondrial stress t... | ACCEPT | Summary: Protease activation following mitochondrial dysfunction is central to OMA1 quality control. Reason: Protease activation following mitochondrial dysfunction is central to OMA1 quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0033554 cellular response to stress | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: Protease activation following mitochondrial dysfunction is central to OMA1 quality control. Reason: Protease activation following mitochondrial dysfunction is central to OMA1 quality control. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0034982 mitochondrial protein processing | IDA PMID:25275009 Activation of mitochondrial protease OMA1 by Bax and Bak pro... | ACCEPT | Summary: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Reason: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0034982 mitochondrial protein processing | IEA GO_REF:0000107 | ACCEPT | Summary: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Reason: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0034982 mitochondrial protein processing | IMP PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | ACCEPT | Summary: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Reason: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:25275009 Activation of mitochondrial protease OMA1 by Bax and Bak pro... | KEEP AS NON CORE | Summary: OPA1 cleavage can facilitate apoptotic remodeling; this downstream outcome is conditional rather than the defining enzyme activity. Reason: OPA1 cleavage can facilitate apoptotic remodeling; this downstream outcome is conditional rather than the defining enzyme activity. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0097009 energy homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Energy homeostasis is a physiological consequence of mitochondrial proteostasis and stress signaling. Reason: Energy homeostasis is a physiological consequence of mitochondrial proteostasis and stress signaling. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Energy homeostasis is a physiological consequence of mitochondrial proteostasis and stress signaling. Reason: Energy homeostasis is a physiological consequence of mitochondrial proteostasis and stress signaling. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cold-induced thermogenesis is a mammalian physiological context downstream of mitochondrial proteostasis; it is not the primary molecular activity. Reason: Cold-induced thermogenesis is a mammalian physiological context downstream of mitochondrial proteostasis; it is not the primary molecular activity. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:22433842 Loss of mitochondrial protease OMA1 alters processing of the... | UNDECIDED | Summary: Cold-induced thermogenesis is a mammalian physiological context downstream of mitochondrial proteostasis; it is not the primary molecular activity. The target-specific support in PMID:22433842 still requires detailed assessment of the experimental results. Reason: Cold-induced thermogenesis is a mammalian physiological context downstream of mitochondrial proteostasis; it is not the primary molecular activity. The target-specific support in PMID:22433842 still requires detailed assessment of the experimental results. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0140467 integrated stress response signaling | IDA PMID:32132706 A pathway coordinated by DELE1 relays mitochondrial stress t... | ACCEPT | Summary: Human OMA1-dependent DELE1 cleavage activates the mitochondrial stress signal to the integrated stress response. Reason: Human OMA1-dependent DELE1 cleavage activates the mitochondrial stress signal to the integrated stress response. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0140467 integrated stress response signaling | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: Human OMA1-dependent DELE1 cleavage activates the mitochondrial stress signal to the integrated stress response. Reason: Human OMA1-dependent DELE1 cleavage activates the mitochondrial stress signal to the integrated stress response. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0140468 HRI-mediated signaling | IDA PMID:32132706 A pathway coordinated by DELE1 relays mitochondrial stress t... | ACCEPT | Summary: Processed DELE1 activates HRI, coupling OMA1 proteolysis to the conserved stress-response pathway. Reason: Processed DELE1 activates HRI, coupling OMA1 proteolysis to the conserved stress-response pathway. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:0140468 HRI-mediated signaling | IDA PMID:32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DE... | ACCEPT | Summary: Processed DELE1 activates HRI, coupling OMA1 proteolysis to the conserved stress-response pathway. Reason: Processed DELE1 activates HRI, coupling OMA1 proteolysis to the conserved stress-response pathway. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:1903850 regulation of cristae formation | IDA PMID:25275009 Activation of mitochondrial protease OMA1 by Bax and Bak pro... | ACCEPT | Summary: Processing of OPA1 influences cristae architecture, connecting protease activity to inner-membrane organization. Reason: Processing of OPA1 influences cristae architecture, connecting protease activity to inner-membrane organization. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:1990627 mitochondrial inner membrane fusion | IEA GO_REF:0000107 | ACCEPT | Summary: OPA1 processing regulates inner-membrane fusion. Participation includes proteolytic regulation and does not mean OMA1 directly fuses bilayers. Reason: OPA1 processing regulates inner-membrane fusion. Participation includes proteolytic regulation and does not mean OMA1 directly fuses bilayers. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
| GO:1990627 mitochondrial inner membrane fusion | ISS GO_REF:0000024 | ACCEPT | Summary: OPA1 processing regulates inner-membrane fusion. Participation includes proteolytic regulation and does not mean OMA1 directly fuses bilayers. Reason: OPA1 processing regulates inner-membrane fusion. Participation includes proteolytic regulation and does not mean OMA1 directly fuses bilayers. Supporting Evidence: file:human/OMA1/OMA1-uniprot.txt CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. |
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Download this section (compressed HTML)The human reference supplies mechanistic evidence for the corresponding selected horse protein; the human conclusion alone is not validation of the horse sequence. The exact horse comparison is in genes/HORSE/OMA1/OMA1-bioinformatics/RESULTS.md. Research reports are source leads; annotation decisions cite the underlying publication or experimentally supported UniProt passages. Unresolved source-specific results retain UNDECIDED.
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