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

被引:124
作者
Paschen, SA
Rothbauer, U
Káldi, K
Bauer, MF
Neupert, W
Brunner, M
机构
[1] Univ Munich, Inst Physiol Chem, D-80336 Munich, Germany
[2] Akad Lehrkrankenhaus Munchen Schwabing, Inst Klin Chem Mol Diagnost & Mitochondriale Gene, D-80804 Munich, Germany
关键词
membrane insertion; mitochondria; protein translocation; TIM8-13; complex; Tim23;
D O I
10.1093/emboj/19.23.6392
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 me show that the TIM8-13 complex interacts with translocation intermediates of Tim23, which are partially translocated across the outer membrane but not,vith 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 TIM18-13 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.
引用
收藏
页码:6392 / 6400
页数:9
相关论文
共 33 条
[11]   A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness [J].
Jin, H ;
May, M ;
Tranebjaerg, L ;
Kendall, E ;
Fontan, G ;
Jackson, J ;
Subramony, SH ;
Arena, F ;
Lubs, H ;
Smith, S ;
Stevenson, R ;
Schwartz, C ;
Vetrie, D .
NATURE GENETICS, 1996, 14 (02) :177-180
[12]   Biogenesis of Tim23 and Tim17, integral components of the TIM machinery for matrix-targeted preproteins [J].
Káldi, K ;
Bauer, MF ;
Sirrenberg, C ;
Neupert, W ;
Brunner, M .
EMBO JOURNAL, 1998, 17 (06) :1569-1576
[13]   The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane [J].
Kerscher, O ;
Holder, J ;
Srinivasan, M ;
Leung, RS ;
Jensen, RE .
JOURNAL OF CELL BIOLOGY, 1997, 139 (07) :1663-1675
[14]   Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins [J].
Koehler, CM ;
Merchant, S ;
Oppliger, W ;
Schmid, K ;
Jarosch, E ;
Dolfini, L ;
Junne, T ;
Schatz, G ;
Tokatlidis, K .
EMBO JOURNAL, 1998, 17 (22) :6477-6486
[15]   Import of mitochondrial carriers mediated by essential proteins of the intermembrane space [J].
Koehler, CM ;
Jarosch, E ;
Tokatlidis, K ;
Schmid, K ;
Schweyen, RJ ;
Schatz, G .
SCIENCE, 1998, 279 (5349) :369-373
[16]   Human deafness dystonia syndrome is a mitochondrial disease [J].
Koehler, CM ;
Leuenberger, D ;
Merchant, S ;
Renold, A ;
Junne, T ;
Schatz, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (05) :2141-2146
[17]   Different import pathways through the mitochondrial intermembrane space for inner membrane proteins [J].
Leuenberger, D ;
Bally, NA ;
Schatz, G ;
Koehler, CM .
EMBO JOURNAL, 1999, 18 (17) :4816-4822
[18]   MPI1, AN ESSENTIAL GENE ENCODING A MITOCHONDRIAL-MEMBRANE PROTEIN, IS POSSIBLY INVOLVED IN PROTEIN IMPORT INTO YEAST MITOCHONDRIA [J].
MAARSE, AC ;
BLOM, J ;
GRIVELL, LA ;
MEIJER, M .
EMBO JOURNAL, 1992, 11 (10) :3619-3628
[19]   EFFICIENT MESSENGER-RNA-DEPENDENT TRANSLATION SYSTEM FROM RETICULOCYTE LYSATES [J].
PELHAM, HRB ;
JACKSON, RJ .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1976, 67 (01) :247-256
[20]   Mitochondrial biogenesis: The Tom and Tim machine [J].
Pfanner, N ;
Meijer, M .
CURRENT BIOLOGY, 1997, 7 (02) :R100-R103