OMA1

Description

The OMA1 (OMA1 zinc metallopeptidase) is a protein-coding gene located on chromosome 1.

Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1 gene. OMA1 is a Zn2+-dependent metalloendopeptidase in the inner membrane of mitochondria. The OMA1 acronym was derived from overlapping proteolytic activity with m-AAA protease 1. The OMA1 protease acts at the intersection of a mitochondrial quality control system and energy metabolism, whereby its activation correlates with outer membrane permeabilization and cytochrome c release in the context of apoptosis. Mammalian OMA1 can cleave the inner-membrane shaping protein OPA1 and the signaling peptide DELE1 in a context-dependent manner.

== Gene == The human OMA1 gene spans with 9 exons 66 kb of the reverse strand of the short arm of chromosome 1 (1p32.2-p32.1). OMA1 is conserved and homologues have been identified in model organisms, such as mice and yeast. Yet, no homologous have been found in C. elegans and drosophila.

== Structure == The human OMA1 protein comprises 524 amino acids. The nuclear encoded protein exhibits an amino-terminal mitochondrial import sequence, which is removed upon import giving rise to a 43.8 kDa mature protease.

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). {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}

OMA1 is also known as 2010001O09Rik, DAB1, MPRP-1, MPRP1, YKR087C, ZMPOMA1, peptidase.

Associated Diseases

WES Whole Exome Sequencing