Human OMA1: Stress-responsive mitochondrial proteolysis

Reference protein: Q96E52. This is a manual literature synthesis using fetched primary-publication text and the reviewed human UniProt record.

Catalysis and immediate substrate

Mammalian-cell knockdown experiments establish OMA1-dependent cleavage of OPA1 after mitochondrial depolarization or ATP loss. Reduced cleavage preserves fusion competence and slows apoptosis. This directly supports proteolysis, metalloendopeptidase activity and mitochondrial protein processing. OMA1 is not itself a membrane fusogen: its control of fusion occurs through substrate processing. PMID:20038677(https://pubmed.ncbi.nlm.nih.gov/20038677/)

Apoptosis and cristae

In an inducible apoptosis system, Bax/Bak-dependent activation of OMA1 promoted OPA1 cleavage and cristae remodeling; OMA1 loss attenuated cytochrome-c release. This is a specific signaling context. It supports a role in apoptosis but should not replace mitochondrial quality control as the central enzyme function. PMID:25275009(https://pubmed.ncbi.nlm.nih.gov/25275009/)

Other substrates and stress signaling

OMA1-mediated cleavage of UQCC3 after depolarization broadens the mitochondrial quality-control substrate set. The OMA1–DELE1 pathway links organelle dysfunction to cytosolic HRI/eIF2alpha integrated stress signaling; cleavage relays the signal rather than OMA1 independently phosphorylating eIF2alpha. PMID:32132706(https://pubmed.ncbi.nlm.nih.gov/32132706/)

Horse transfer limits

The horse comparison preserves the HExxH catalytic motif and the third zinc ligand. Terminal regions are more variable, so exact targeting and processing positions should not simply be copied from human coordinates. Broad proteolysis is well grounded; identical cleavage kinetics and complete substrate repertoire are not established. PMID:20038677(https://pubmed.ncbi.nlm.nih.gov/20038677/)

Evidence access and research scope

The source caches distinguish full text from abstract-only access; unresolved experimental annotations should remain UNDECIDED until their supporting material is available. This synthesis focuses on the biochemical mechanism, localization, and evidence needed for the paired horse prediction assessment; it does not certify every existing GO annotation.