OPA1 is a dynamin-related mechanochemical GTPase of the mitochondrial inner membrane, imported via an N-terminal presequence and anchored by a transmembrane segment with its GTPase, stalk and lipid-binding paddle domains in the intermembrane space. Alternative splicing and proteolytic processing by the inner-membrane proteases YME1L and OMA1 generate long, membrane-anchored (L-OPA1) and short, soluble (S-OPA1) forms. L-OPA1 on one membrane and cardiolipin on the opposing membrane are sufficient for GTP hydrolysis-dependent fusion of inner membranes, which follows mitofusin-mediated outer-membrane fusion, and S-OPA1 enhances this reaction. Independently of fusion, OPA1 oligomers bend cardiolipin-rich membranes and, with the MICOS complex, maintain crista junctions and cristae architecture, which supports respiratory efficiency, retains cytochrome c within cristae and so restrains apoptosis, and contributes to mtDNA maintenance. Heterozygous OPA1 mutations cause autosomal dominant optic atrophy, sometimes with multisystem "plus" features and mtDNA deletions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000266 mitochondrial fission | TAS PMID:12509422 Loss of OPA1 perturbates the mitochondrial inner membrane st... | REMOVE | Summary: Mitochondrial fission (TAS) based on fragmentation of the mitochondrial network after OPA1 knockdown. Reason: Fragmentation after OPA1 loss reflects loss of inner-membrane fusion with ongoing DRP1-mediated fission, not a role of OPA1 in fission; the cited abstract describes OPA1 as an inner-membrane organizer. OPA1 is a fusion GTPase and the annotation is contradicted by the mechanism. Supporting Evidence: PMID:12509422 down-regulation of OPA1 in HeLa cells using specific small interfering RNA (siRNA) leads to fragmentation of the mitochondrial network PMID:12509422 These results suggest that OPA1 is a major organizer of the mitochondrial inner membrane from which the maintenance of the cristae integrity depends. |
| GO:0000287 magnesium ion binding | NAS PMID:11017080 OPA1, encoding a dynamin-related GTPase, is mutated in autos... | MARK AS OVER ANNOTATED | Summary: Magnesium ion binding (NAS) from the OPA1 gene identification paper. Reason: Mg2+ is the catalytic cofactor of the dynamin G domain together with GTP; this is implicit in GTPase activity and was not specifically shown for OPA1 in the cited paper. Supporting Evidence: PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | EXP PMID:28628083 Molecular basis of selective mitochondrial fusion by heterot... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | EXP PMID:28746876 WBSCR16 Is a Guanine Nucleotide Exchange Factor Important fo... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:27667664 A Genome-wide CRISPR Death Screen Identifies Genes Essential... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:32245890 The short variant of optic atrophy 1 (OPA1) improves cell su... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:32379273 Structural insights into G domain dimerization and pathogeni... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:37612504 Structural mechanism of mitochondrial membrane remodelling b... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IDA PMID:37612506 OPA1 helical structures give perspective to mitochondrial dy... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0003924 GTPase activity | TAS PMID:11017080 OPA1, encoding a dynamin-related GTPase, is mutated in autos... | ACCEPT | Summary: GTPase activity. Purified OPA1 (S-OPA1, L-OPA1 and G-domain constructs) hydrolyses GTP; activity is stimulated by cardiolipin-containing liposomes and drives membrane remodelling and fusion. Reason: Core molecular function, directly shown in many studies and consistent with its dynamin-type G domain (IBA, InterPro/RHEA). Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. PMID:32228866 Basal and liposome binding induced GTPase activity of wild type S-OPA1 and its EMB domain mutants. PMID:32379273 The GTPase activity of various OPA1 constructs was measured in the presence of 250 mM NaCl or KCl and 4 mM MgCl2. PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0005515 protein binding | IPI PMID:20436456 The BH3-only Bnip3 binds to the dynamin Opa1 to promote mito... | REMOVE | Summary: IPI with BNIP3, which binds OPA1 to disrupt OPA1 complexes and promote fragmentation/apoptosis (abstract only cached). Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. |
| GO:0005515 protein binding | IPI PMID:21081504 ChChd3, an inner mitochondrial membrane protein, is essentia... | REMOVE | Summary: IPI with IMMT (MIC60/mitofilin), a MICOS core subunit; OPA1 and MICOS cooperate at crista junctions. Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005515 protein binding | IPI PMID:21364629 Vital function of PRELI and essential requirement of its LEA... | REMOVE | Summary: IPI with PRELID1 (abstract only cached). Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:21364629 PRELI interacts with OPA1 to maintain mitochondria structures intact |
| GO:0005515 protein binding | IPI PMID:24282027 Functional interaction of Parkinson's disease-associated LRR... | REMOVE | Summary: IPI with LRRK2 from co-IP of overexpressed proteins. Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:24282027 Myc-tagged Drp1, Mfn1, Mfn2 and OPA1 interact with FLAG-LRRK2 following IP with anti-myc antibody. |
| GO:0005515 protein binding | IPI PMID:24344202 SIRT3 deacetylates and activates OPA1 to regulate mitochondr... | REMOVE | Summary: IPI with SIRT3, which deacetylates OPA1 and increases its GTPase activity. Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. The relationship is that OPA1 is a SIRT3 substrate. Supporting Evidence: PMID:24344202 The mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating its GTPase activity. |
| GO:0005515 protein binding | IPI PMID:28746876 WBSCR16 Is a Guanine Nucleotide Exchange Factor Important fo... | REMOVE | Summary: IPI with RCC1L (WBSCR16), proposed as a guanine nucleotide exchange factor for OPA1. Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. OPA1 is the GEF client, not the bearer of a binding function here. Supporting Evidence: PMID:28746876 the most straightforward interpretation of the in vitro GTP hydrolysis results is that WBSCR16 is a GEF that acts to load OPA1 with GTP, thus providing more opportunity for intrinsic OPA1 GTPase activity |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | REMOVE | Summary: IPI with LRRK2 from co-IP of overexpressed proteins. Reason: Generic protein binding is uninformative; no more specific OPA1 molecular function follows from this interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:24282027 Myc-tagged Drp1, Mfn1, Mfn2 and OPA1 interact with FLAG-LRRK2 following IP with anti-myc antibody. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding (InterPro). Reason: Correct; OPA1 binds GTP via its dynamin-type G domain. Supporting Evidence: PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoplasm (IBA from a dynamin-superfamily node). Reason: Formally true (mitochondria are within the cytoplasm), but OPA1 resides inside mitochondria in the intermembrane space and inner membrane; uninformative. Supporting Evidence: PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP, HPA, IDA, IEA). Reason: Correct, less specific than inner membrane/intermembrane space. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:11017079 encodes a dynamin-related protein localized to mitochondria |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrion (HTP, HPA, IDA, IEA). Reason: Correct, less specific than inner membrane/intermembrane space. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:11017079 encodes a dynamin-related protein localized to mitochondria |
| GO:0005739 mitochondrion | IDA PMID:17545159 Mitochondrial fission and fusion mediators, hFis1 and OPA1, ... | ACCEPT | Summary: Mitochondrion (HTP, HPA, IDA, IEA). Reason: Correct, less specific than inner membrane/intermembrane space. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:11017079 encodes a dynamin-related protein localized to mitochondria |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: Mitochondrion (HTP, HPA, IDA, IEA). Reason: Correct, less specific than inner membrane/intermembrane space. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:11017079 encodes a dynamin-related protein localized to mitochondria |
| GO:0005741 mitochondrial outer membrane | IDA PMID:12504110 Differential sublocalization of the dynamin-related protein ... | KEEP AS NON CORE | Summary: Mitochondrial outer membrane (IDA): in sucrose-gradient fractionation one processed OPA1 form co-fractionated with outer membranes (abstract only cached). Reason: OPA1 is imported into the intermembrane space and anchored in, or peripherally associated with, the inner membrane; outer-membrane co-fractionation likely reflects contact sites. Not contradicted outright, but not the functional location. Supporting Evidence: PMID:12504110 the 88-kDa protein predominantly associates with the mitochondrial outer membrane, on the contrary, the 93-kDa protein associates with the inner membrane PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. |
| GO:0005743 mitochondrial inner membrane | EXP PMID:11017079 Nuclear gene OPA1, encoding a mitochondrial dynamin-related ... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:16778770 Regulation of mitochondrial morphology through proteolytic c... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:20974897 OPA1 links human mitochondrial genome maintenance to mtDNA r... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:28746876 WBSCR16 Is a Guanine Nucleotide Exchange Factor Important fo... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:37612504 Structural mechanism of mitochondrial membrane remodelling b... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:37612506 OPA1 helical structures give perspective to mitochondrial dy... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | NAS PMID:20436456 The BH3-only Bnip3 binds to the dynamin Opa1 to promote mito... | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-8867344 | ACCEPT | Summary: Mitochondrial inner membrane. L-OPA1 is anchored in the inner membrane by an N-terminal transmembrane segment after import, and S-OPA1 associates peripherally with it on the intermembrane-space side. Reason: Core location, supported experimentally and by ISS/IEA/Reactome. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:28746876 most WBSCR16 was shown, like OPA1, to localize to the outer face of the inner membrane |
| GO:0005758 mitochondrial intermembrane space | EXP PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | EXP PMID:37612504 Structural mechanism of mitochondrial membrane remodelling b... | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | EXP PMID:37612506 OPA1 helical structures give perspective to mitochondrial dy... | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:17008324 Mitochondrial functions and estrogen receptor-dependent nucl... | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005758 mitochondrial intermembrane space | ISS PMID:11847212 Primary structure of a dynamin-related mouse mitochondrial G... | ACCEPT | Summary: Mitochondrial intermembrane space. OPA1 faces the intermembrane space; S-OPA1 is a peripheral IMS-side protein. Reason: Correct; consistent with the inner-membrane topology. Supporting Evidence: PMID:12504110 Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:21081504 ChChd3 interacts preferentially with the soluble IMS form of OPA1. |
| GO:0005874 microtubule | IBA GO_REF:0000033 | REMOVE | Summary: Microtubule (IBA from a dynamin-superfamily node). Reason: OPA1 is located inside mitochondria (intermembrane space/inner membrane) and is topologically separated from cytosolic microtubules; the term is propagated from classical dynamin. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000170013 SUPPORTS SOURCE BUT NOT TARGET Dynamin-superfamily root node seeded by classical dynamin/plant DRP microtubule data; OPA1 resides in the mitochondrial intermembrane space and cannot contact cytosolic microtubules. Supporting Evidence: PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space |
| GO:0007005 mitochondrion organization | IEA GO_REF:0000117 | ACCEPT | Summary: Mitochondrion organization (ARBA, IMP, NAS), including mtDNA stability and mitochondrial morphology defects in OPA1 mutants. Reason: Correct general parent of OPA1 roles in fusion and cristae organization. Supporting Evidence: PMID:18158317 thus revealing an unrecognized role of the OPA1 protein in mtDNA stability PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion |
| GO:0007005 mitochondrion organization | IMP PMID:18158317 OPA1 mutations induce mitochondrial DNA instability and opti... | ACCEPT | Summary: Mitochondrion organization (ARBA, IMP, NAS), including mtDNA stability and mitochondrial morphology defects in OPA1 mutants. Reason: Correct general parent of OPA1 roles in fusion and cristae organization. Supporting Evidence: PMID:18158317 thus revealing an unrecognized role of the OPA1 protein in mtDNA stability PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion |
| GO:0007005 mitochondrion organization | IMP PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | ACCEPT | Summary: Mitochondrion organization (ARBA, IMP, NAS), including mtDNA stability and mitochondrial morphology defects in OPA1 mutants. Reason: Correct general parent of OPA1 roles in fusion and cristae organization. Supporting Evidence: PMID:18158317 thus revealing an unrecognized role of the OPA1 protein in mtDNA stability PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion |
| GO:0007005 mitochondrion organization | NAS PMID:11017080 OPA1, encoding a dynamin-related GTPase, is mutated in autos... | ACCEPT | Summary: Mitochondrion organization (ARBA, IMP, NAS), including mtDNA stability and mitochondrial morphology defects in OPA1 mutants. Reason: Correct general parent of OPA1 roles in fusion and cristae organization. Supporting Evidence: PMID:18158317 thus revealing an unrecognized role of the OPA1 protein in mtDNA stability PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion |
| GO:0007007 inner mitochondrial membrane organization | IDA PMID:12509422 Loss of OPA1 perturbates the mitochondrial inner membrane st... | ACCEPT | Summary: Inner mitochondrial membrane organization: OPA1 knockdown disorganizes cristae. Reason: Core process; OPA1 organizes the inner membrane both by fusion and by maintaining crista junctions. Supporting Evidence: PMID:12509422 These results suggest that OPA1 is a major organizer of the mitochondrial inner membrane from which the maintenance of the cristae integrity depends. PMID:28628083 a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure |
| GO:0007007 inner mitochondrial membrane organization | IEA GO_REF:0000107 | ACCEPT | Summary: Inner mitochondrial membrane organization: OPA1 knockdown disorganizes cristae. Reason: Core process; OPA1 organizes the inner membrane both by fusion and by maintaining crista junctions. Supporting Evidence: PMID:12509422 These results suggest that OPA1 is a major organizer of the mitochondrial inner membrane from which the maintenance of the cristae integrity depends. PMID:28628083 a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure |
| GO:0007601 visual perception | IMP PMID:11017080 OPA1, encoding a dynamin-related GTPase, is mutated in autos... | KEEP AS NON CORE | Summary: Visual perception (IMP), based on OPA1 mutations causing autosomal dominant optic atrophy. Reason: Disease association reflects retinal ganglion cell vulnerability to mitochondrial dysfunction; OPA1 has no visual-perception-specific function. Supporting Evidence: PMID:11017080 Because most mutations probably represent null alleles, dominant inheritance of the disease may result from haploinsufficiency of OPA1. |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | REMOVE | Summary: Microtubule binding (IBA from a dynamin-superfamily node). Reason: OPA1 is an intramitochondrial protein with no access to microtubules; the activity belongs to classical dynamins. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000170013 SUPPORTS SOURCE BUT NOT TARGET Node seeded by Drosophila shibire; microtubule binding not applicable to an intermembrane-space protein. Supporting Evidence: PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space |
| GO:0008053 mitochondrial fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0008053 mitochondrial fusion | IDA PMID:17545159 Mitochondrial fission and fusion mediators, hFis1 and OPA1, ... | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0008053 mitochondrial fusion | IEA GO_REF:0000107 | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0008053 mitochondrial fusion | IMP PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0008053 mitochondrial fusion | IMP PMID:20436456 The BH3-only Bnip3 binds to the dynamin Opa1 to promote mito... | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0008053 mitochondrial fusion | TAS PMID:12509422 Loss of OPA1 perturbates the mitochondrial inner membrane st... | ACCEPT | Summary: Mitochondrial fusion. OPA1 is the inner-membrane fusion GTPase; it is essential for fusion together with the mitofusins. Reason: Core process, supported by multiple experiments and IBA/IEA/TAS. Supporting Evidence: PMID:21149567 In mammals, mitofusin proteins (Mfn1 and Mfn2) of MOM and the inner membrane protein Opa1 are essential for mitochondrial fusion PMID:20436456 Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. PMID:37612504 The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane |
| GO:0010821 regulation of mitochondrion organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of mitochondrion organization (ARBA). Reason: Not wrong but less precise than the direct roles in inner-membrane fusion and cristae formation. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Membrane (HDA, NK cell membrane proteome; abstract only). Reason: Correct but uninformative; OPA1 is an inner-membrane protein. |
| GO:0016559 peroxisome fission | IBA GO_REF:0000033 | REMOVE | Summary: Peroxisome fission (IBA). Reason: OPA1 is imported into mitochondria and acts in the intermembrane space; there is no evidence for OPA1 on peroxisomes or in peroxisome division, which is mediated by DNM1L. The IBA is propagated from a node whose descendants with peroxisome evidence are fission dynamins (DNM1L/Dnm1/Vps1). Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN008520527 SUPPORTS SOURCE BUT NOT TARGET Node evidence comes from fission dynamins (mouse Dnm1l, yeast Dnm1/Vps1); does not apply to the intramitochondrial fusion GTPase OPA1. Supporting Evidence: PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space |
| GO:0019896 axonal transport of mitochondrion | TAS PMID:11017080 OPA1, encoding a dynamin-related GTPase, is mutated in autos... | MARK AS OVER ANNOTATED | Summary: Axonal transport of mitochondrion (TAS) from the OPA1 gene identification paper. Reason: The cited abstract does not address mitochondrial transport; OPA1 acts inside mitochondria and any transport defects in neurons would be secondary. Supporting Evidence: PMID:11017080 identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases |
| GO:0030061 mitochondrial crista | IDA PMID:12504110 Differential sublocalization of the dynamin-related protein ... | ACCEPT | Summary: Mitochondrial crista (IDA). Reason: OPA1 localizes to the cristae inner membrane and crista junctions. Supporting Evidence: PMID:12509422 anchored to the mitochondrial cristae inner membrane, facing the intermembrane space PMID:32567732 OPA1 works in concert with the Mic10βsubcomplex to stabilize tubular CJs |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendrite (ISS/IEA from mouse): mOPA1 is seen in neuronal dendrites, i.e. in dendritic mitochondria. Reason: Reflects mitochondrial distribution in neurons, not a dendrite-specific function. Supporting Evidence: PMID:11847212 Within dissociated cerebellar cells, mOPA1 protein was clearly observed in the dendrites and somas of neuronal cells |
| GO:0030425 dendrite | ISS PMID:11847212 Primary structure of a dynamin-related mouse mitochondrial G... | KEEP AS NON CORE | Summary: Dendrite (ISS/IEA from mouse): mOPA1 is seen in neuronal dendrites, i.e. in dendritic mitochondria. Reason: Reflects mitochondrial distribution in neurons, not a dendrite-specific function. Supporting Evidence: PMID:11847212 Within dissociated cerebellar cells, mOPA1 protein was clearly observed in the dendrites and somas of neuronal cells |
| GO:0031966 mitochondrial membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial membrane (IBA). Reason: Correct; OPA1 is an inner-membrane protein. Supporting Evidence: PMID:16778770 During import, the matrix-targeting signal is removed and processed forms (L-isoforms) are anchored to the inner membrane in type I topology. |
| GO:0032740 positive regulation of interleukin-17 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of interleukin-17 production (ISS/IEA from mouse T-cell studies). Reason: Downstream of OPA1-dependent mitochondrial cristae/metabolism in Th17 cells; non-core. |
| GO:0032740 positive regulation of interleukin-17 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of interleukin-17 production (ISS/IEA from mouse T-cell studies). Reason: Downstream of OPA1-dependent mitochondrial cristae/metabolism in Th17 cells; non-core. |
| GO:0042407 cristae formation | IEA GO_REF:0000107 | ACCEPT | Summary: Cristae formation: OPA1 loss disrupts cristae and crista junctions; OPA1 acts with MICOS to stabilize crista junctions. Reason: Core process, a second function separable from fusion (S-OPA1 maintains cristae without fusion activity). Supporting Evidence: PMID:33130824 indicating that OPA1 regulates mitochondrial crista formation and dynamics PMID:32567732 OPA1 works in concert with the Mic10βsubcomplex to stabilize tubular CJs PMID:32245890 S-OPA1, despite its inability to mediate mitochondrial fusion, is fully competent for maintaining cristae structure and energetic activity through its GTPase activity PMID:28628083 a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure |
| GO:0042407 cristae formation | IMP PMID:32567732 MICOS assembly controls mitochondrial inner membrane remodel... | ACCEPT | Summary: Cristae formation: OPA1 loss disrupts cristae and crista junctions; OPA1 acts with MICOS to stabilize crista junctions. Reason: Core process, a second function separable from fusion (S-OPA1 maintains cristae without fusion activity). Supporting Evidence: PMID:33130824 indicating that OPA1 regulates mitochondrial crista formation and dynamics PMID:32567732 OPA1 works in concert with the Mic10βsubcomplex to stabilize tubular CJs PMID:32245890 S-OPA1, despite its inability to mediate mitochondrial fusion, is fully competent for maintaining cristae structure and energetic activity through its GTPase activity PMID:28628083 a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure |
| GO:0042407 cristae formation | IMP PMID:33130824 OPA1 and MICOS Regulate mitochondrial crista dynamics and fo... | ACCEPT | Summary: Cristae formation: OPA1 loss disrupts cristae and crista junctions; OPA1 acts with MICOS to stabilize crista junctions. Reason: Core process, a second function separable from fusion (S-OPA1 maintains cristae without fusion activity). Supporting Evidence: PMID:33130824 indicating that OPA1 regulates mitochondrial crista formation and dynamics PMID:32567732 OPA1 works in concert with the Mic10βsubcomplex to stabilize tubular CJs PMID:32245890 S-OPA1, despite its inability to mediate mitochondrial fusion, is fully competent for maintaining cristae structure and energetic activity through its GTPase activity PMID:28628083 a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:12509422 Loss of OPA1 perturbates the mitochondrial inner membrane st... | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (IDA): OPA1 loss triggers cytochrome c release and apoptosis. Reason: OPA1 restrains apoptosis by keeping crista junctions closed and cytochrome c sequestered; a consequence of its cristae role. Supporting Evidence: PMID:12509422 As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration |
| GO:0046039 GTP metabolic process | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | MARK AS OVER ANNOTATED | Summary: GTP metabolic process (IDA) from GTP hydrolysis assays. Reason: GTP hydrolysis by a mechanochemical GTPase is captured by GTPase activity; it is not participation in GTP metabolism. Supporting Evidence: PMID:20185555 Enhancement of GTP hydrolysis activity of wild-type OPA1 by liposomes. |
| GO:0051259 protein complex oligomerization | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | KEEP AS NON CORE | Summary: Protein complex oligomerization (IDA): OPA1 assembles into arrays on liposomes. Reason: Self-assembly is part of the mechanism rather than a separate role. Supporting Evidence: PMID:20185555 Electron microscopy clearly indicates that OPA1-S1 assembles on the outer surface of the tubular protrusions, resulting in a membrane topology that is similar to that of classical dynamins. PMID:37612504 OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells |
| GO:0061025 membrane fusion | IEA GO_REF:0000108 | ACCEPT | Summary: Membrane fusion (IEA inferred from GTPase-dependent fusogenic activity). Reason: Correct; OPA1 fuses inner membranes. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion |
| GO:0070300 phosphatidic acid binding | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | KEEP AS NON CORE | Summary: Phosphatidic acid binding (IDA): OPA1-S1 binds PA- and PS-containing liposomes in vitro. Reason: In vitro binding to anionic lipids; cardiolipin is the physiologically relevant lipid partner. Supporting Evidence: PMID:20185555 We found that OPA1-S1 associates strongly with liposomes containing 25% phosphatidic acid (POPA) or 25% phosphoserine (POPS), and these interactions also enhance GTP hydrolysis |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of release of cytochrome c from mitochondria (IMP, IEA). Reason: Follows from OPA1 maintaining tight crista junctions that sequester cytochrome c; non-core consequence of cristae organization. Supporting Evidence: PMID:21149567 Cristae are thought to trap large pools of cytochrome c, and down-regulation of Opa1 may lead to the opening of cristae junctions and mobilization of cytochrome c PMID:12509422 As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | IMP PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | KEEP AS NON CORE | Summary: Negative regulation of release of cytochrome c from mitochondria (IMP, IEA). Reason: Follows from OPA1 maintaining tight crista junctions that sequester cytochrome c; non-core consequence of cristae organization. Supporting Evidence: PMID:21149567 Cristae are thought to trap large pools of cytochrome c, and down-regulation of Opa1 may lead to the opening of cristae junctions and mobilization of cytochrome c PMID:12509422 As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration |
| GO:0090398 cellular senescence | IDA PMID:17545159 Mitochondrial fission and fusion mediators, hFis1 and OPA1, ... | MARK AS OVER ANNOTATED | Summary: Cellular senescence (IDA): co-depletion of OPA1 with FIS1 suppresses senescence-like changes caused by FIS1 loss. Reason: Indirect: the effect is explained by restoring mitochondrial fragmentation; OPA1 does not act in a senescence pathway. Supporting Evidence: PMID:17545159 depletion of both hFis1 and OPA1, a critical component of mitochondrial fusion, resulted in extensive mitochondrial fragmentation and markedly rescued cells from senescence-associated phenotypic changes |
| GO:0097749 membrane tubulation | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | KEEP AS NON CORE | Summary: Membrane tubulation (IDA): S-OPA1 assembles on and tubulates cardiolipin-containing liposomes. Reason: Directly shown in vitro; a mechanistic manifestation of its membrane-remodelling activity. Supporting Evidence: PMID:20185555 Electron microscopy clearly indicates that OPA1-S1 assembles on the outer surface of the tubular protrusions, resulting in a membrane topology that is similar to that of classical dynamins. PMID:32228866 Tubulation activity of wild type S-OPA1 and its EMB domain mutants examined by negative stain electron microscopy. |
| GO:0097749 membrane tubulation | IDA PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | KEEP AS NON CORE | Summary: Membrane tubulation (IDA): S-OPA1 assembles on and tubulates cardiolipin-containing liposomes. Reason: Directly shown in vitro; a mechanistic manifestation of its membrane-remodelling activity. Supporting Evidence: PMID:20185555 Electron microscopy clearly indicates that OPA1-S1 assembles on the outer surface of the tubular protrusions, resulting in a membrane topology that is similar to that of classical dynamins. PMID:32228866 Tubulation activity of wild type S-OPA1 and its EMB domain mutants examined by negative stain electron microscopy. |
| GO:0140523 GTPase-dependent fusogenic activity | IDA PMID:28628083 Molecular basis of selective mitochondrial fusion by heterot... | ACCEPT | Summary: GTPase-dependent fusogenic activity: L-OPA1 on one membrane and cardiolipin on the other are sufficient for GTP hydrolysis-dependent fusion in vitro. Reason: Core molecular function, demonstrated by in vitro reconstitution and structural studies. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:28628083 GTP-independent membrane tethering through L-OPA1 and CL primes the subsequent GTP-hydrolysis-dependent fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:37612504 OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells |
| GO:0140523 GTPase-dependent fusogenic activity | IDA PMID:37612504 Structural mechanism of mitochondrial membrane remodelling b... | ACCEPT | Summary: GTPase-dependent fusogenic activity: L-OPA1 on one membrane and cardiolipin on the other are sufficient for GTP hydrolysis-dependent fusion in vitro. Reason: Core molecular function, demonstrated by in vitro reconstitution and structural studies. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:28628083 GTP-independent membrane tethering through L-OPA1 and CL primes the subsequent GTP-hydrolysis-dependent fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:37612504 OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells |
| GO:0140523 GTPase-dependent fusogenic activity | IEA GO_REF:0000107 | ACCEPT | Summary: GTPase-dependent fusogenic activity: L-OPA1 on one membrane and cardiolipin on the other are sufficient for GTP hydrolysis-dependent fusion in vitro. Reason: Core molecular function, demonstrated by in vitro reconstitution and structural studies. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:28628083 GTP-independent membrane tethering through L-OPA1 and CL primes the subsequent GTP-hydrolysis-dependent fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:37612504 OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells |
| GO:0180020 membrane bending activity | IDA PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | ACCEPT | Summary: Membrane bending activity: OPA1 inserts a paddle-domain loop into cardiolipin membranes and its helical lattices bend membranes. Reason: Directly shown by cryo-EM/cell studies; underlies cristae shaping. Supporting Evidence: PMID:37612504 Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. PMID:37612504 the membrane-bending OPA1 oligomer undergoes conformational changes that pull the membrane-inserting loop out of the outer leaflet PMID:37612506 Helical Assemblies of s-OPA1 coating cardiolipin containing membranes with and without GDP-AlFx. |
| GO:0180020 membrane bending activity | IDA PMID:37612504 Structural mechanism of mitochondrial membrane remodelling b... | ACCEPT | Summary: Membrane bending activity: OPA1 inserts a paddle-domain loop into cardiolipin membranes and its helical lattices bend membranes. Reason: Directly shown by cryo-EM/cell studies; underlies cristae shaping. Supporting Evidence: PMID:37612504 Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. PMID:37612504 the membrane-bending OPA1 oligomer undergoes conformational changes that pull the membrane-inserting loop out of the outer leaflet PMID:37612506 Helical Assemblies of s-OPA1 coating cardiolipin containing membranes with and without GDP-AlFx. |
| GO:1901612 cardiolipin binding | IDA PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have def... | ACCEPT | Summary: Cardiolipin binding: OPA1 binds cardiolipin through its paddle domain; cardiolipin stimulates GTP hydrolysis and is required in trans for heterotypic fusion. Reason: Well supported and functionally essential. Supporting Evidence: PMID:37612504 Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion |
| GO:1901612 cardiolipin binding | IDA PMID:28628083 Molecular basis of selective mitochondrial fusion by heterot... | ACCEPT | Summary: Cardiolipin binding: OPA1 binds cardiolipin through its paddle domain; cardiolipin stimulates GTP hydrolysis and is required in trans for heterotypic fusion. Reason: Well supported and functionally essential. Supporting Evidence: PMID:37612504 Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion |
| GO:1901612 cardiolipin binding | IDA PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | ACCEPT | Summary: Cardiolipin binding: OPA1 binds cardiolipin through its paddle domain; cardiolipin stimulates GTP hydrolysis and is required in trans for heterotypic fusion. Reason: Well supported and functionally essential. Supporting Evidence: PMID:37612504 Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. PMID:20185555 OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of ER stress-induced intrinsic apoptotic signaling (IGI with Parkin/NEMO; IEA). Reason: Parkin-NF-kB signalling upregulates OPA1 for stress protection; OPA1 acts through maintaining mitochondrial integrity, non-core. Supporting Evidence: PMID:23453807 the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IGI PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Negative regulation of ER stress-induced intrinsic apoptotic signaling (IGI with Parkin/NEMO; IEA). Reason: Parkin-NF-kB signalling upregulates OPA1 for stress protection; OPA1 acts through maintaining mitochondrial integrity, non-core. Supporting Evidence: PMID:23453807 the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | REMOVE | Summary: Axon cytoplasm (IEA, GO_REF:0000108, inferred from the axonal transport annotation). Reason: OPA1 is an intramitochondrial protein; the inference depends on the weak axonal-transport TAS row and places OPA1 in a compartment where it does not reside as such. |
| GO:1990627 mitochondrial inner membrane fusion | IDA PMID:28628083 Molecular basis of selective mitochondrial fusion by heterot... | ACCEPT | Summary: Mitochondrial inner membrane fusion: L-OPA1 (with S-OPA1 enhancing efficiency) mediates IMM fusion in reconstituted systems and cells. Reason: Core process. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:32228866 Both L-OPA1 and S-OPA1 participate in mitochondrial inner membrane fusion. |
| GO:1990627 mitochondrial inner membrane fusion | IDA PMID:31922487 Two forms of Opa1 cooperate to complete fusion of the mitoch... | ACCEPT | Summary: Mitochondrial inner membrane fusion: L-OPA1 (with S-OPA1 enhancing efficiency) mediates IMM fusion in reconstituted systems and cells. Reason: Core process. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:32228866 Both L-OPA1 and S-OPA1 participate in mitochondrial inner membrane fusion. |
| GO:1990627 mitochondrial inner membrane fusion | IDA PMID:32228866 Cryo-EM structures of S-OPA1 reveal its interactions with me... | ACCEPT | Summary: Mitochondrial inner membrane fusion: L-OPA1 (with S-OPA1 enhancing efficiency) mediates IMM fusion in reconstituted systems and cells. Reason: Core process. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:32228866 Both L-OPA1 and S-OPA1 participate in mitochondrial inner membrane fusion. |
| GO:1990627 mitochondrial inner membrane fusion | IEA GO_REF:0000107 | ACCEPT | Summary: Mitochondrial inner membrane fusion: L-OPA1 (with S-OPA1 enhancing efficiency) mediates IMM fusion in reconstituted systems and cells. Reason: Core process. Supporting Evidence: PMID:28628083 L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion PMID:31922487 As observed by the Langer group, l-Opa1 alone in our system, is indeed sufficient for full fusion, albeit at very low levels PMID:32228866 Both L-OPA1 and S-OPA1 participate in mitochondrial inner membrane fusion. |
| GO:2000330 positive regulation of T-helper 17 cell lineage commitment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of T-helper 17 cell lineage commitment (ISS/IEA from mouse). Reason: Metabolic consequence of OPA1 function in T cells; non-core. |
| GO:2000330 positive regulation of T-helper 17 cell lineage commitment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of T-helper 17 cell lineage commitment (ISS/IEA from mouse). Reason: Metabolic consequence of OPA1 function in T cells; non-core. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of intrinsic apoptotic signaling pathway (IEA from mouse). Reason: Consequence of cristae/cytochrome c sequestration; non-core. Supporting Evidence: PMID:12509422 As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration |
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Download this section (compressed HTML)Q: How do L-OPA1 and S-OPA1 ratios, set by YME1L and OMA1, tune the balance between inner-membrane fusion and cristae maintenance in vivo?
Q: Why are retinal ganglion cells selectively vulnerable to OPA1 haploinsufficiency?
Experiment: In situ cryo-ET of crista junctions in cells expressing only L-OPA1 or S-OPA1 to determine the oligomeric arrangement responsible for junction stability versus fusion.
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