Stress-induced OMA1-mediated cleavage of AIFM1 suppresses cell growth by controlling mitochondrial OXPHOS activity

ABSTRACT: Mitochondrial proteases regulate dynamic properties of organelle morphology and ensure functional plasticity at the cellular level. The metalloprotease OMA1 mediates constitutive and stress-inducible processing of its mitochondrial substrates, although only a few of its direct functional targets have been characterized. Using in vitro and in vivo multi-proteomic and biochemical approaches, we here demonstrate that the membrane-anchored intermembrane space (IMS) protein AIFM1 serves as a mitochondrial stress-responsive OMA1 substrate. Under stress conditions, OMA1 cleaves AIFM1 in the IMS with slower kinetics than its conventional substrate, the dynamin-like GTPase OPA1. OMA1-mediated dislocation of cleaved AIFM1 from the mitochondrial inner membrane reduces its interaction with oxidative p

SUBMITTER: Takumi Koshiba 

PROVIDER: S-SCDT-10_1038-S44318-026-00734-Y | biostudies-other |

REPOSITORIES: biostudies-other