In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins.

Institut fuer Biochemie und Molekularbiologie, Zentrum fuer Biochemie und Molekulare Zellforschung, 79104 Freiburg, Germany.
The intermembrane space of mitochondria accommodates the essential mitochondrial intermembrane space assembly (MIA) machinery that catalyzes oxidative folding of proteins. The disulfide bond formation pathway is based on a relay of reactions involving disulfide transfer from the sulfhydryl oxidase Erv1 to Mia40 and from Mia40 to substrate proteins. However, the substrates of the MIA typically contain two disulfide bonds. It was unclear what the mechanisms are that ensure that proteins are released from Mia40 in a fully oxidized form. In this work, we dissect the stage of the oxidative folding relay, in which Mia40 binds to its substrate. We identify dynamics of the Mia40-substrate intermediate complex. Our experiments performed in a native environment, both in organello and in vivo, show that Erv1 directly participates in Mia40-substrate complex dynamics by forming a ternary complex. Thus Mia40 in cooperation with Erv1 promotes the formation of two disulfide bonds in the substrate protein, ensuring the efficiency of oxidative folding in the intermembrane space of mitochondria.
Mesh Terms:
Binding Sites, Cysteine, Mitochondrial Membrane Transport Proteins, Mitochondrial Membranes, Mitochondrial Proteins, Multiprotein Complexes, Mutation, Oxidation-Reduction, Oxidoreductases Acting on Sulfur Group Donors, Phenotype, Protein Binding, Protein Conformation, Protein Precursors, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity
Mol. Biol. Cell Oct. 01, 2012; 23(20);3957-69 [PUBMED:22918950]
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