title: The role of the TIM8-13 complex in the import of Tim23 into mitochondria.
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.
authors: Institut für Physiologische Chemie der Universität München, Goethestrasse 33, 80336 München, Germany.
authors: S A
authors: SA
authors: Paschen
authors: U
authors: U
authors: Rothbauer
authors: K
authors: K
authors: Káldi
authors: M F
authors: MF
authors: Bauer
authors: W
authors: W
authors: Neupert
authors: M
authors: M
authors: Brunner
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D013577:Syndrome; D013696:Temperature; D014357:Trypsin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C403093:TIM13 protein, S cerevisiae; C083081:TIM23 protein, S cerevisiae; C485737:TIMM13 protein, human; C118122:TIMM8A protein, human; D014357:Trypsin; D015032:Zinc