OMA1
OMA1 (OMA1 Zinc Metallopeptidase) is a Protein Coding gene. Diseases associated with OMA1 include 3-Methylglutaconic Aciduria, Type Iii. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Glucose / Energy Metabolism. Gene Ontology (GO) annotations related to this gene include metalloendopeptidase activity.
Function
Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, PubMed:32132706, PubMed:32132707).
Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, PubMed:25275009, PubMed:32132706, PubMed:32132707).
Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion (PubMed:20038677, PubMed:25275009).
Also acts as a regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage of OPA1, leading to the remodeling of mitochondrial cristae and allowing the release of cytochrome c from mitochondrial cristae (PubMed:25275009).
In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome (PubMed:30733118).
May also cleave UQCC3 in response to mitochondrial depolarization (PubMed:25605331).
Also acts as an activator of the integrated stress response (ISR): in response to mitochondrial stress, mediates cleavage of DELE1 to generate the processed form of DELE1 (S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (PubMed:32132706, PubMed:32132707).
Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions (By similarity).
Binds cardiolipin, possibly regulating its protein turnover (By similarity).
Required for the stability of the respiratory supercomplexes (By similarity).
Biological Process
Cristae formationIEA:Ensembl
Diet induced thermogenesisISS:UniProtKB
Energy homeostasisISS:UniProtKB
Glucose metabolic processISS:UniProtKB
HRI-mediated signalingManual Assertion Based On ExperimentIDA:UniProtKB
Integrated stress response signalingManual Assertion Based On ExperimentIDA:UniProtKB
Lipid metabolic processISS:UniProtKB
Mitochondrial protein processingManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrial respiratory chain complex assemblyISS:UniProtKB
Negative regulation of mitochondrial fusionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Protein autoprocessingISS:UniProtKB
Protein quality control for misfolded or incompletely synthesized proteinsManual Assertion Based On ExperimentIMP:UniProtKB
Proteolysis involved in cellular protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Regulation of apoptotic processTAS:Reactome
Regulation of cristae formationManual Assertion Based On ExperimentIDA:UniProtKB
Zymogen activationISS:UniProtKB
PTM
May form a redox-dependent disulfide bond (By similarity).
Exists in a semi-oxidized state and is activated by prolonged hypoxia (PubMed:31044600).
Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1) (By similarity).
Autocatalytic processing at the C-terminus takes place at residues 447-456 (By similarity).
The S-OMA1 form is unstable (By similarity).
Degradaded by YMEL1 in response to membrane depolarization (PubMed:26923599).
Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (By similarity).