title: The mitochondrial presequence translocase: an essential role of Tim50 in directing preproteins to the import channel.
abstract: Mitochondrial proteins with N-terminal targeting signals are transported across the inner membrane via the presequence translocase, which consists of membrane-integrated channel proteins and the matrix Hsp70 import motor. It has not been known how preproteins are directed to the import channel. We have identified the essential protein Tim50, which exposes its major domain to the intermembrane space. Tim50 interacts with preproteins in transit and directs them to the channel protein Tim23. Inactivation of Tim50 strongly inhibits the import of preproteins with a classical matrix-targeting signal, while preproteins carrying an additional inner membrane-sorting signal do not strictly depend on Tim50. Thus, Tim50 is crucial for guiding the precursors of matrix proteins to their insertion site in the inner membrane.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geissler
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
authors.forename: Kaye N
authors.initials: KN
authors.lastname: Truscott
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.forename: Katrin
authors.initials: K
authors.lastname: Brandner
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae; C469615:TIM50 protein, S cerevisiae