The zinc-binding protein Hot13 promotes oxidation of the mitochondrial import receptor Mia40
The zinc-binding protein Hot13 promotes oxidation of the mitochondrial import receptor Mia40
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DOI：
10.1038/embor.2008.173
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发表时间：
2008-11-01
期刊：
影响因子：
7.7
通讯作者：
Herrmann, Johannes M.
中科院分区：
文献类型：
--
作者：
Mesecke, Nikola;Bihlmaier, Karl;Herrmann, Johannes M.
二硫化物中继系统介导含半胱氨酸的蛋白质进入线粒体的膜间隙。该系统由两种必需蛋白质Mia40和Erv1组成，它们通过二硫键转移与新输入的蛋白质结合。第三个组分，Hot13，被认为在膜间隙富含半胱氨酸的蛋白质的生物合成中很重要，但Hot13的分子功能仍不清楚。在这里，我们表明，热13，一个保守的锌结合蛋白，相互作用的功能和物理与进口受体Mia40。它在体内和体外均改善Mia40的Erv1依赖性氧化。因此，在缺乏Hot13的突变体中，Mia40的底物的输入受损，特别是在锌离子的存在下。在线粒体以及在体外，热13可以在功能上被锌结合螯合剂取代。我们建议，热13保持Mia40在无锌状态，从而促进其有效的氧化Erv1。
A disulphide relay system mediates the import of cysteine-containing proteins into the intermembrane space of mitochondria. This system consists of two essential proteins, Mia40 and Erv1, which bind to newly imported proteins by disulphide transfer. A third component, Hot13, was proposed to be important in the biogenesis of cysteine-rich proteins of the intermembrane space, but the molecular function of Hot13 remained unclear. Here, we show that Hot13, a conserved zinc-binding protein, interacts functionally and physically with the import receptor Mia40. It improves the Erv1-dependent oxidation of Mia40 both in vivo and in vitro. As a consequence, in mutants lacking Hot13, the import of substrates of Mia40 is impaired, particularly in the presence of zinc ions. In mitochondria as well as in vitro, Hot13 can be functionally replaced by zinc-binding chelators. We propose that Hot13 maintains Mia40 in a zinc-free state, thereby facilitating its efficient oxidation by Erv1.