Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1. 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 (By similarity). 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. In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome. May also cleave UQCC3 in response to mitochondrial depolarization. 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 (By similarity). 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. Binds cardiolipin, possibly regulating its protein turnover. Required for the stability of the respiratory supercomplexes (By similarity). Binds 1 zinc ion per subunit. Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization. Homooligomer. The stress-sensor region regulates proteolysis and activation. Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1). Autocatalytic processing at the C-terminus takes place at residues 447-456. The S-OMA1 form is unstable (By similarity). Degradaded by YMEL1 in response to membrane depolarization (By similarity). Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (By similarity). May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity). Belongs to the peptidase M48 family.