Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria
Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria
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DOI：
10.1093/emboj/cdg485
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发表时间：
2003-10-01
期刊：
影响因子：
11.4
通讯作者：
Hell, K
中科院分区：
文献类型：
--
作者：
Mokranjac, D;Sichting, M;Hell, K
TIM23转位酶介导依赖于DeltaPsi和ATP的蛋白质进入线粒体。我们鉴定TIM14是TIM23转位酶的一个新组分。Tim14是内膜的一个完整蛋白，具有一个典型的J结构域，暴露在基质空间中。TIM14基因存在于几乎所有真核生物的基因组中。在酵母中，Tim14是生存所必需的。缺乏Tim14的细胞线粒体在TIM23复合体介导的蛋白质输入方面存在缺陷。特别是，需要mtHsp70作用的蛋白质的进口受到影响。Tim14以依赖于ATP的方式与Tim44和mtHsp70相互作用。TIM14的J结构域的HPD基序的突变是致命的。因此，Tim14是线粒体输入马达的一个组成部分。我们提出了一个模型，在这个模型中，mtHsp70的激活需要Tim14，并使这个伴侣在Tim44介导的捕获进入基质的未折叠前蛋白的过程中以一种快速和受调控的方式发挥作用。
The TIM23 translocase mediates the DeltaPsi- and ATP-dependent import of proteins into mitochondria. We identified Tim14 as a novel component of the TIM23 translocase. Tim14 is an integral protein of the inner membrane with a typical J-domain exposed to the matrix space. TIM14 genes are present in the genomes of virtually all eukaryotes. In yeast, Tim14 is essential for viability. Mitochondria from cells depleted of Tim14 are deficient in the import of proteins mediated by the TIM23 complex. In particular, import of proteins that require the action of mtHsp70 is affected. Tim14 interacts with Tim44 and mtHsp70 in an ATP-dependent manner. A mutation in the HPD motif of the J-domain of Tim14 is lethal. Thus, Tim14 is a constituent of the mitochondrial import motor. We propose a model in which Tim14 is required for the activation of mtHsp70 and enables this chaperone to act in a rapid and regulated manner in the Tim44-mediated trapping of unfolded preproteins entering the matrix.