In response to depolarization of the inner membrane or apoptotic stimulus, OMA1 cleaves itself to yield an activated form, S-OMA1, which is then degraded (inferred from the mouse homolog). The response of OMA1 to depolarization requires an N-terminal hydrophobic region of OMA1 and an adjacent positively charged region (inferred from the mouse homolog). Cleavage occurs between residues 447 and 456 (443 and 452 of mouse OMA1, Zhang et al. 2014). The activated OMA1 cleaves OPA1, a regulator of mitochondrial fusion; YME1L1, an inner membrane protease; and, probably, DELE1, which transits to the cytosol to activate the integrated stress response (Fessler et al. 2020, Guo et al. 2020).