αβ'-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import
αβ'-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import
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DOI：
10.1111/febs.14024
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发表时间：
2017-03-01
期刊：
影响因子：
5.4
通讯作者：
Funes, Soledad
中科院分区：
文献类型：
--
作者：
Carlos Ponce-Rojas, Jose;Clara Avendano-Monsalve, Maria;Funes, Soledad
线粒体蛋白质组主要由核编码蛋白组成。这些多肽是用信号合成的，这些信号引导它们在细胞内运输到细胞器表面，然后在不同的线粒体亚室内，直到它们到达它们的功能目的地。有研究表明，新生多肽相关复合体(NAC)--一种识别翻译活性核糖体上新生链的胞浆伴侣--在核编码的线粒体蛋白的输入中发挥了作用。然而，调控NAC介导的共翻译输入的分子机制仍然不清楚。在这里，我们证明了酿酒酵母中由α和β‘亚基形成的一个特定的NAC异源二聚体特异性地参与了线粒体的输入过程，并在功能上与分选和组装机械复合体的外膜蛋白亚基Sam37合作。这两个组分中的突变体都显示出生长缺陷，在细胞质中错误地积累了线粒体蛋白质的前体形式，并且线粒体蛋白质含量发生了变化。我们认为，α-β‘-NAC和Sam37是在线粒体蛋白质合成的早期阶段识别线粒体蛋白质的系统成员，护送它们到线粒体的输入机制。
The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial subcompartments until they reach their functional destination. It has been suggested that the nascent-polypeptide associated complex (NAC) - a cytosolic chaperone that recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated cotranslational import are still not clear. Here, we show that a particular NAC heterodimer formed by subunits alpha and beta' in Saccharomyces cerevisiae is specifically involved in the process of mitochondrial import and functionally cooperates with Sam37, an outer membrane protein subunit of the sorting and assembly machinery complex. Mutants in both components display growth defects, incorrectly accumulate precursor forms of mitochondrial proteins in the cytosol, and have an altered mitochondrial protein content. We propose that alpha beta'-NAC and Sam37 are members of the system that recognizes mitochondrial proteins at early stages of their synthesis, escorting them to the import machinery of mitochondria.