title: Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5.
abstract: Import of nuclear-encoded precursor proteins into mitochondria and their subsequent sorting into mitochondrial subcompartments is mediated by translocase enzymes in the mitochondrial outer and inner membranes. Precursor proteins carrying amino-terminal targeting signals are translocated into the matrix by the integral inner membrane proteins Tim23 and Tim17 in cooperation with Tim44 and mitochondrial Hsp70. We describe here the discovery of a new pathway for the transport of members of the mitochondrial carrier family and other inner membrane proteins that contain internal targeting signals. Two related proteins in the intermembrane space, Tim10/Mrs11 and Tim12/Mrs5, interact sequentially with these precursors and facilitate their translocation across the outer membrane, irrespective of the membrane potential. Tim10 and Tim12 are found in a complex with Tim22, which takes over the precursor and mediates its membrane-potential-dependent insertion into the inner membrane. This interaction of Tim10 and Tim12 with the precursors depends on the presence of divalent metal ions. Both proteins contain a zinc-finger-like motif with four cysteines and bind equimolar amounts of zinc ions.
authors.affiliation: Institut für Physiologische Chemie der Universität München, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sirrenberg
authors.forename: M
authors.initials: M
authors.lastname: Endres
authors.forename: H
authors.initials: H
authors.lastname: Fölsch
authors.forename: R A
authors.initials: RA
authors.lastname: Stuart
authors.forename: W
authors.initials: W
authors.lastname: Neupert
authors.forename: M
authors.initials: M
authors.lastname: Brunner
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002413:Cations, Divalent; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D005656:Fungal Proteins / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008670:Metals / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D002352:Carrier Proteins; D002413:Cations, Divalent; D003432:Cross-Linking Reagents; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008670:Metals; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C107250:TIM10 protein, S cerevisiae; C100674:TIM12 protein, S cerevisiae; C102549:TIM22 protein, S cerevisiae; D000226:Mitochondrial ADP, ATP Translocases