Kutik Stephan, Rissler Michael, Guan Xue Li, Guiard Bernard, Shui Guanghou, Gebert Natalia, Heacock Philip N, Rehling Peter, Dowhan William, Wenk Markus R, Pfanner Nikolaus, Wiedemann Nils
Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Universität Freiburg, 79104 Freiburg, Germany.
J Cell Biol. 2008 Dec 29;183(7):1213-21. doi: 10.1083/jcb.200806048.
The mitochondrial inner membrane contains different translocator systems for the import of presequence-carrying proteins and carrier proteins. The translocator assembly and maintenance protein 41 (Tam41/mitochondrial matrix protein 37) was identified as a new member of the mitochondrial protein translocator systems by its role in maintaining the integrity and activity of the presequence translocase of the inner membrane (TIM23 complex). Here we demonstrate that the assembly of proteins imported by the carrier translocase, TIM22 complex, is even more strongly affected by the lack of Tam41. Moreover, respiratory chain supercomplexes and the inner membrane potential are impaired by lack of Tam41. The phenotype of Tam41-deficient mitochondria thus resembles that of mitochondria lacking cardiolipin. Indeed, we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin. The pleiotropic effects of the translocator maintenance protein on preprotein import and respiratory chain can be attributed to its role in biosynthesis of mitochondrial cardiolipin.
线粒体内膜含有不同的转运体系统,用于导入携带前导序列的蛋白质和载体蛋白。转运体组装与维持蛋白41(Tam41/线粒体基质蛋白37)因其在维持内膜前导序列转位酶(TIM23复合物)的完整性和活性中的作用,被鉴定为线粒体蛋白转运体系统的一个新成员。在此我们证明,载体转位酶TIM22复合物导入的蛋白质组装受Tam41缺失的影响更大。此外,呼吸链超复合物和内膜电位因Tam41缺失而受损。因此,Tam41缺陷型线粒体的表型类似于缺乏心磷脂的线粒体。事实上,我们发现Tam41是二聚体磷脂心磷脂生物合成所必需的。转运体维持蛋白对前体蛋白导入和呼吸链的多效性作用可归因于其在线粒体心磷脂生物合成中的作用。