Impaired folding of the mitochondrial small TIM chaperones induces clearance by the i-AAA protease

Abstract

The intermembrane space of mitochondria contains a dedicated chaperone network - the small translocase of the inner membrane (TIM) family - for the sorting of hydrophobic precursors. All small TIMs are defined by the presence of a twin CX3C motif and the monomeric proteins are stabilized by two intramolecular disulfide bonds formed between the cysteines of these motifs. The conserved cysteine residues within small TIM members have also been shown to participate in early biogenesis events, with the most N-terminal cysteine residue important for import and retention within the intermembrane space via the receptor and disulfide oxidase, Mia40. In this study, we have analyzed the in vivo consequ..