title: The disulfide relay system of mitochondria is connected to the respiratory chain.
abstract: All proteins of the intermembrane space of mitochondria are encoded by nuclear genes and synthesized in the cytosol. Many of these proteins lack presequences but are imported into mitochondria in an oxidation-driven process that relies on the activity of Mia40 and Erv1. Both factors form a disulfide relay system in which Mia40 functions as a receptor that transiently interacts with incoming polypeptides via disulfide bonds. Erv1 is a sulfhydryl oxidase that oxidizes and activates Mia40, but it has remained unclear how Erv1 itself is oxidized. Here, we show that Erv1 passes its electrons on to molecular oxygen via interaction with cytochrome c and cytochrome c oxidase. This connection to the respiratory chain increases the efficient oxidation of the relay system in mitochondria and prevents the formation of toxic hydrogen peroxide. Thus, analogous to the system in the bacterial periplasm, the disulfide relay in the intermembrane space is connected to the electron transport chain of the inner membrane.
authors.affiliation: Department of Cell Biology, University of Kaiserslautern, Kaiserslautern 67663, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Bihlmaier
authors.forename: Nikola
authors.initials: N
authors.lastname: Mesecke
authors.forename: Nadia
authors.initials: N
authors.lastname: Terziyska
authors.forename: Melanie
authors.initials: M
authors.lastname: Bien
authors.forename: Kai
authors.initials: K
authors.lastname: Hell
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
mesh_terms: D000818:Animals; D003579:Cytochrome Reductases / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D006736:Horses; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: C507282:CHCHD4 protein, human; D004220:Disulfides; C495320:MIA40 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; C073790:ERV1 protein, S cerevisiae; D003576:Electron Transport Complex IV; D010100:Oxygen