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
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