Oxidation-driven protein import into mitochondria: Insights and blind spots.
The intermembrane space of mitochondria contains a dedicated machinery for the introduction of disulfide bonds into proteins. In this case, oxidative protein folding is believed to drive the vectorial translocation of polypeptides after their synthesis in the cytosol across the mitochondrial outer membrane. Substrates of this system are recognized by a hydrophobic binding cleft of the oxidoreductase Mia40 which converts them into an oxidized stably folded conformation. Mia40 is maintained in an oxidized, active conformation by the sulfhydryl oxidase Erv1, a homodimeric flavoenzyme, which can form disulfide bonds de novo. Erv1 passes electrons on to cytochrome c and further to the respiratory chain. The components of this system, their structures and the mechanisms of disulfide bond formation were analyzed only very recently. This review discusses our knowledge about this system as well as open questions which still wait to be addressed. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.
Riemer
Jan
J
Cell Biology, University of Kaiserslautern, Erwin-Schrödinger-Straße 13, 67663 Kaiserslautern, Germany.
Fischer
Manuel
M
Herrmann
Johannes M
JM
D000818:Animals; D004579:Electron Transport / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D021381:Protein Transport
D024101:Mitochondrial Proteins