The role of the TIM8-13 complex in the import of Tim23 into mitochondria

EMBO J. 2000 Dec 1;19(23):6392-400. doi: 10.1093/emboj/19.23.6392.

Abstract

Tim8 and Tim13 are non-essential, conserved proteins of the mitochondrial intermembrane space, which are organized in a hetero-oligomeric complex. They are structurally related to Tim9 and Tim10, essential components of the import machinery for mitochondrial carrier proteins. Here we show that the TIM8-13 complex interacts with translocation intermediates of Tim23, which are partially translocated across the outer membrane but not with fully imported or assembled Tim23. The TIM8-13 complex binds to the N-terminal or intermediate domain of Tim23. It traps the incoming precursor in the intermembrane space thereby preventing retrograde translocation. The TIM8-13 complex is strictly required for import of Tim23 under conditions when a low membrane potential exists in the mitochondria. The human homologue of Tim8 is encoded by the DDP1 (deafness/dystonia peptide 1) gene, which is associated with the Mohr-Tranebjaerg syndrome (MTS), a progressive neurodegenerative disorder leading to deafness. It is demonstrated that import of human Tim23 is dependent on a high membrane potential. A mechanism to explain the pathology of MTS is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology*
  • Cell Membrane / metabolism
  • Cross-Linking Reagents / pharmacology
  • Humans
  • Male
  • Membrane Potentials
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mitochondria, Liver / metabolism*
  • Mitochondrial Membrane Transport Proteins*
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Models, Biological
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Proteins / metabolism
  • Rats
  • Saccharomyces cerevisiae Proteins*
  • Syndrome
  • Temperature
  • Trypsin / pharmacology
  • Zinc / pharmacology

Substances

  • Carrier Proteins
  • Cross-Linking Reagents
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • TIM13 protein, S cerevisiae
  • TIM23 protein, S cerevisiae
  • TIMM13 protein, human
  • TIMM8A protein, human
  • Trypsin
  • Zinc