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.

Full Name

OMA1 Zinc Metallopeptidase

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

Cellular Location

Mitochondrion inner membrane

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).