Early fate decision for mitochondrially encoded proteins by a molecular triage

Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems either promote the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. Although well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially encoded proteins, key subunits of the oxidative phosphorylation (OXPHOS) system. Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial protein biogenesis and quality control. Conserved prohibitin (PHB)/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in the vicinity of the mitoribosomal tunnel exit allows for a prompt decision on whether newly synthesized proteins are fed into OXPHOS assembly or are degraded.

Automated summary

This study investigates the folding and quality control mechanism of mitochondrially encoded proteins. Dedicated hubs in proximity to the mitoribosomal tunnel exits coordinate the biogenesis and quality control of mitochondrial proteins. The fate of newly synthesized proteins is determined by the conserved prohibitin/m-AAA protease supercomplexes and the availability of assembly chaperones through molecular triaging.