Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5

Nature. 1998 Feb 26;391(6670):912-5. doi: 10.1038/36136.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Carrier Proteins / metabolism*
  • Cations, Divalent
  • Cloning, Molecular
  • Cross-Linking Reagents
  • Fungal Proteins / metabolism*
  • Intracellular Membranes / metabolism
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Metals / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial ADP, ATP Translocases / metabolism
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Molecular Sequence Data
  • Protein Precursors / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*

Substances

  • Carrier Proteins
  • Cations, Divalent
  • Cross-Linking Reagents
  • Fungal Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Metals
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Protein Precursors
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • TIM10 protein, S cerevisiae
  • TIM12 protein, S cerevisiae
  • TIM22 protein, S cerevisiae
  • Mitochondrial ADP, ATP Translocases