OPA1 (Homo sapiens)
- Synonyms: OPA1
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Dynamin-like 120 kDa protein, mitochondrial Precursor (Optic atrophy protein 1) [Contains Dynamin-like 120 kDa protein, form S1] [Source:UniProtKB/Swiss-Prot;Acc:O60313]
- Family: other
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment:
- WIKI: OPA1-H_sapiens
- Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization.
- Yamaguchi R, Lartigue L, Perkins G, Scott RT, Dixit A, Kushnareva Y, Kuwana T, Ellisman MH, Newmeyer DD
- Controversy surrounds the role and mechanism of mitochondrial cristae remodeling in apoptosis. Here we show that the proapoptotic BH3-only proteins Bid and Bim induced full cytochrome c release but only a subtle alteration of crista junctions, which involved the disassembly of Opa1 complexes. Both mitochondrial outer membrane permeabilization (MOMP) and crista junction opening (CJO) were caspase independent and required a functional BH3 domain and Bax/Bak. However, MOMP and CJO were experimentally separable. Pharmacological blockade of MOMP did not prevent Opa1 disassembly and CJO; moreover, expression of a disassembly-resistant mutant Opa1 (Q297V) blocked cytochrome c release and apoptosis but not Bax activation. Thus, apoptosis requires a subtle form of Opa1-dependent crista remodeling that is induced by BH3-only proteins and Bax/Bak but independent of MOMP. Mol Cell. 2008 Aug 22;31(4):557-69. Epub 2008 Aug 7.
- Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation.
- Arnoult D, Grodet A, Lee YJ, Estaquier J, Blackstone C
- Mitochondria are important participants in apoptosis, releasing cytochrome c into the cytoplasm and undergoing extensive fragmentation. However, mechanisms underlying these processes remain unclear. Here, we demonstrate that cytochrome c release during apoptosis precedes mitochondrial fragmentation. Unexpectedly, OPA1, a dynamin-like GTPase of the mitochondrial intermembrane space important for maintaining cristae structure, is co-released with cytochrome c. To mimic the loss of OPA1 occurring after its release, we knocked down OPA1 expression using RNA interference. This triggered structural changes in the mitochondrial cristae and caused increased fragmentation by blocking mitochondrial fusion. Because cytochrome c is mostly sequestered within cristae folds but released rapidly and completely during apoptosis, we examined the effect of OPA1 loss on cytochrome c release, demonstrating that it is accelerated. Thus, our results suggest that an initial mitochondrial leak of OPA1 leads to cristae structural alterations and exposure of previously sequestered protein pools, permitting continued release in a feed-forward manner to completion. Moreover, our findings indicate that the resulting OPA1 depletion causes a block in mitochondrial fusion, providing a compelling mechanism for the prominent increase in mitochondrial fragmentation seen during apoptosis. J Biol Chem. 2005 Oct 21;280(42):35742-50. Epub 2005 Aug 22.
Structure & Sequence [+]
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Homologs list [+]
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0050896||response to stimulus||biological_proccess||IEA|
|GO:0019896||axon transport of mitochondrion||biological_proccess||TAS|
|GO:0007007||inner mitochondrial membrane organization||biological_proccess||IDA|
|GO:0045768||positive regulation of anti-apoptosis||biological_proccess||IDA|
|GO:0000287||magnesium ion binding||mollecular_function||NAS|
|GO:0016021||integral to membrane||cell_component||IEA|
|GO:0005741||mitochondrial outer membrane||cell_component||IDA|
|GO:0005758||mitochondrial intermembrane space||cell_component||ISS|
Check GO Evidence Codes here
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
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