MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation
MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation
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DOI：
10.1016/j.cell.2012.11.053
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发表时间：
2012-12-21
期刊：
影响因子：
64.5
通讯作者：
Rehling, Peter
中科院分区：
文献类型：
--
作者：
Mick, David U.;Dennerlein, Sven;Rehling, Peter
线粒体复合链由双重遗传来源的亚基在专门的组装因子的辅助下组装而成。核心亚基在线粒体核糖体上翻译，而其他亚基在胞质翻译后输入。如何将导入的亚基引导到含有p2p编码亚基的组装中间体中还没有解决。在这里，我们报告了一个全面的解剖早期细胞色素c氧化酶组装中间体包含正常线粒体翻译所需的蛋白质，并揭示组装因子促进人类的合成链复合物的生物合成。我们发现，TIM21，一个亚基的内膜前序列转位酶，也存在于主要的装配中间体含有新的合成和进口的martina的合成链亚基，我们称之为MITRAC复合物。人TIM 21是蛋白质输入的关键，但需要将早期组装的含前序列的亚基整合到合成链中间体中。我们建立了一个意想不到的TIM23运输机械和装配的装配链复合物，调节线粒体蛋白质合成，响应其组装状态之间的分子联系。
Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.