Tom40 functions as a channel for protein retrotranslocation in the mitochondria-associated degradation (MAD) pathway.

ABSTRACT: The mitochondria-associated degradation pathway (MAD) mediates removal and elimination of damaged, unfolded mitochondrial proteins by the ubiquitin-proteasome system (UPS). Previous studies revealed that MAD is critical for mitochondrial protein quality control and that MAD function extends beyond mitochondrial outer membrane (MOM) to proteins within the organelle. Here, we reconstitute retrotranslocation of MAD substrates from the mitochondrial matrix across mitochondrial inner and outer membranes in cell-free systems. This retrotranslocation is ATP-dependent but membrane potential-independent. We also identify a role for the TOM complex, the protein import channel in the MOM, in this process. Inhibition of protein translocation across the Tom40p channel reduces the retrotranslocation of

SUBMITTER: Liao PC 

PROVIDER: S-EPMC12307905 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature