AIM32 is a dual-localized 2Fe-2S mitochondrial protein that functions in redox quality control

ABSTRACT: Maintaining redox homeostasis under normal and stress conditions in the mitochondrion is complex. We used mass spectrometry analysis to identify key proteins that interacted with the sulfhydryl oxidase Erv1 of the mitochondrial intermembrane space assembly (MIA) pathway. Results: Aim32, a thioredoxin-like [2Fe-2S] ferredoxin protein, was identified as an Erv1 binding partner. Aim32 interacted with additional proteins including redox protein Osm1 as well as protein import components Tim17, Tim23, and Tim22. Detailed and complementary localization studies showed that Aim32 resided in both the mitochondrial matrix and intermembrane space, placing it in a rare protein class that is dual-localized within mitochondria. Deletion of Aim32 or conserved cysteine residues that coordinate the Fe-S center resulted in an increased accumulation of proteins with aberrant disulfide linkages. In addition, the steady-state level of assembled TIM22, TIM23, and Oxa1 protein import complexes was decreased and a subset of the import complexes showed misassembly, among other phenotypes. Aim32 also bound to several mitochondrial proteins under non-reducing conditions, suggesting a function in maintaining the redox status of oxidized proteins by potentially targeting cysteine residues that may be sensitive to oxidation. Finally, Aim32 was required for growth in stress conditions and the mitochondrial genome was essential in strains that lacked Aim32. Innovation: Aim32 is uniquely localized to both the mitochondrial intermembrane space and matrix and functions in redox regulation with a potential role in quality control. Conclusion: Aim32 may be poised as a sensor to maintain the redox state by repairing oxidized cysteine residues in a broad range of mitochondrial proteins.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Yasaman Jami-Alahmadi  

LAB HEAD: Deepa Dabir

PROVIDER: PXD021662 | Pride | 2022-02-16

REPOSITORIES: Pride