title: Mitochondrial OXA Translocase Plays a Major Role in Biogenesis of Inner-Membrane Proteins.
abstract: The mitochondrial inner membrane harbors three protein translocases. Presequence translocase and carrier translocase are essential for importing nuclear-encoded proteins. The oxidase assembly (OXA) translocase is required for exporting mitochondrial-encoded proteins; however, different views exist about its relevance for nuclear-encoded proteins. We report that OXA plays a dual role in the biogenesis of nuclear-encoded mitochondrial proteins. First, a systematic analysis of OXA-deficient mitochondria led to an unexpected expansion of the spectrum of OXA substrates imported via the presequence pathway. Second, biogenesis of numerous metabolite carriers depends on OXA, although they are not imported by the presequence pathway. We show that OXA is crucial for the biogenesis of the Tim18-Sdh3 module of the carrier translocase. The export translocase OXA is thus required for the import of metabolite carriers by promoting assembly of the carrier translocase. We conclude that OXA is of central importance for the biogenesis of the mitochondrial inner membrane.
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Sebastian B
authors.initials: SB
authors.lastname: Stiller
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Höpker
authors.affiliation: Institute of Biology II, Biochemistry - Functional Proteomics, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Conny
authors.initials: C
authors.lastname: Schütze
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Schrempp
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Vent-Schmidt
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Horvath
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Frazier
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gebert
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bohnert
authors.affiliation: Institute of Biology II, Biochemistry - Functional Proteomics, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: nikolaus.pfanner@biochemie.uni-freiburg.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: nils.wiedemann@biochemie.uni-freiburg.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D029701:Saccharomyces cerevisiae Proteins; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV