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.
Summary: The human OPA1-cleavage experiments and conserved horse HExxH motif/third zinc ligand support metalloendopeptidase activity.
Reason: The human OPA1-cleavage experiments and conserved horse HExxH motif/third zinc ligand support metalloendopeptidase activity. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: The human OPA1-cleavage experiments and conserved horse HExxH motif/third zinc ligand support metalloendopeptidase activity.
Reason: The human OPA1-cleavage experiments and conserved horse HExxH motif/third zinc ligand support metalloendopeptidase activity. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: OMA1 is an inner-mitochondrial-membrane protease; the horse protein retains the catalytic membrane-protease architecture.
Reason: OMA1 is an inner-mitochondrial-membrane protease; the horse protein retains the catalytic membrane-protease architecture. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: OMA1 is an inner-mitochondrial-membrane protease; the horse protein retains the catalytic membrane-protease architecture.
Reason: OMA1 is an inner-mitochondrial-membrane protease; the horse protein retains the catalytic membrane-protease architecture. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: OMA1 catalyzes cleavage of protein substrates including OPA1.
Reason: OMA1 catalyzes cleavage of protein substrates including OPA1. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: Mitochondrial inner membrane specifies the conserved location.
Reason: Mitochondrial inner membrane specifies the conserved location. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: Protease activation following mitochondrial dysfunction is central to OMA1 quality control.
Reason: Protease activation following mitochondrial dysfunction is central to OMA1 quality control. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Summary: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing.
Reason: OPA1 and other mitochondrial substrates undergo OMA1-dependent processing. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
GO:0043065 positive regulation of apoptotic process
IEA GO_REF:0000107
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
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. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
Core Functions
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.
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}.
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence.
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 1 ProtNLM GO predictions for the selected horse OMA1 protein, using mammalian experimental findings and an explicit comparison of the horse sequence.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human-cell experiments establish OMA1-dependent proteolytic cleavage of OPA1 (PMID:20038677). The horse sequence retains the HExxH catalytic motif and third zinc ligand, despite more variable terminal regions and 66.47% overall paired identity. The broad proteolysis prediction is a justified transfer of the conserved metalloprotease mechanism and exactly overlaps horse GOA. Specific substrate or stress-response claims would require their own assessment. Training-set membership is unknown.
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}."
file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md: "The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues) with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence and 97.08% of the horse sequence."
PMID:20038677: "In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function."
📚 Additional Documentation
Notes
(OMA1-notes.md)
OMA1: paired evidence notes
Human reference: https://www.uniprot.org/uniprotkb/Q96E52/entry
In this study, we show that this inducible cleavage is mediated by a zinc metalloprotease called OMA1. We find that OMA1 small interfering RNA inhibits inducible cleavage, helps retain fusion competence, and slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and function.
The horse sequence comparison is in OMA1-bioinformatics/RESULTS.md. Transfer is assessed for this exact accession; human biochemical evidence is not equine experimental validation.