title: The mitochondrial ADP/ATP carrier associates with the inner membrane presequence translocase in a stoichiometric manner.
abstract: The majority of mitochondrial proteins are synthesized with amino-terminal signal sequences. The presequence translocase of the inner membrane (TIM23 complex) mediates the import of these preproteins. The essential TIM23 core complex closely cooperates with partner protein complexes like the presequence translocase-associated import motor and the respiratory chain. The inner mitochondrial membrane also contains a large number of metabolite carriers, but their association with preprotein translocases has been controversial. We performed a comprehensive analysis of the TIM23 interactome based on stable isotope labeling with amino acids in cell culture. Subsequent biochemical studies on identified partner proteins showed that the mitochondrial ADP/ATP carrier associates with the membrane-embedded core of the TIM23 complex in a stoichiometric manner, revealing an unexpected connection of mitochondrial protein biogenesis to metabolite transport. Our data indicate that direct TIM23-AAC coupling may support preprotein import into mitochondria when respiratory activity is low.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Carola S
authors.initials: CS
authors.lastname: Mehnert
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Rampelt
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gebert
authors.affiliation: Institut für Biologie II, Fakultät für Biologie, Funktionelle Proteomik, and Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Universität Freiburg, 79104 Freiburg, Germany and.
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Schrempp
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Lioba
authors.initials: L
authors.lastname: Kochbeck
authors.affiliation: Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.affiliation: Institut für Biologie II, Fakultät für Biologie, Funktionelle Proteomik, and Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Universität Freiburg, 79104 Freiburg, Germany and.
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Universität Freiburg, 79104 Freiburg, Germany and. Electronic address: martin.van.der.laan@biochemie.uni-freiburg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
mesh_terms: D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae
keywords: Membrane Protein; Metabolite Carrier; Mitochondria; Mitochondrial Protein Import; Protein Translocation; Respiratory Chain; SILAC; TIM23 Complex; energy Metabolism