Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins.
Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins.
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DOI：
10.1083/jcb.201712029
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发表时间：
2018-09-03
期刊：
影响因子：
--
通讯作者：
Rapaport D
中科院分区：
文献类型：
--
作者：
Jores T;Lawatscheck J;Beke V;Franz-Wachtel M;Yunoki K;Fitzgerald JC;Macek B;Endo T;Kalbacher H;Buchner J;Rapaport D
线粒体β桶蛋白从细胞质输入到细胞器中。Jores等人通过描述一系列与新合成的β-桶蛋白相关的胞质分子伴侣和辅分子伴侣，并确保其最佳的生物发生，为该过程的早期事件提供了新的见解。线粒体β桶蛋白在细胞核中编码，由胞质核糖体翻译，然后输入细胞器。最近，对β-桶蛋白的线粒体内输入途径有了详细的了解。相比之下，新合成的β-桶蛋白如何以可输入构象到达线粒体表面仍然完全不清楚。在这项研究中，我们表明，胞质Hsp 70伴侣和它们的Hsp 40辅助伴侣Ydj 1和Sis 1与新合成的β-桶蛋白相互作用。这些相互作用对于适当的生物发生是高度相关的，因为抑制胞质Hsp 70的活性，防止其与线粒体受体Tom 70对接，或者耗尽Ydj 1和Sis 1导致这些底物进入线粒体的进口显著减少。进一步的实验表明，β-桶蛋白和Hsp 70分子伴侣之间的相互作用及其重要性在哺乳动物细胞中也是保守的。总的来说，这项研究概述了线粒体外膜β桶蛋白生物发生早期事件的新机制。
Mitochondrial β-barrel proteins are imported from the cytosol into the organelle. Jores et al. provide new insights into the early events of this process by describing an array of cytosolic chaperones and cochaperones that associate with newly synthesized β-barrel proteins and assure their optimal biogenesis. Mitochondrial β-barrel proteins are encoded in the nucleus, translated by cytosolic ribosomes, and then imported into the organelle. Recently, a detailed understanding of the intramitochondrial import pathway of β-barrel proteins was obtained. In contrast, it is still completely unclear how newly synthesized β-barrel proteins reach the mitochondrial surface in an import-competent conformation. In this study, we show that cytosolic Hsp70 chaperones and their Hsp40 cochaperones Ydj1 and Sis1 interact with newly synthesized β-barrel proteins. These interactions are highly relevant for proper biogenesis, as inhibiting the activity of the cytosolic Hsp70, preventing its docking to the mitochondrial receptor Tom70, or depleting both Ydj1 and Sis1 resulted in a significant reduction in the import of such substrates into mitochondria. Further experiments demonstrate that the interactions between β-barrel proteins and Hsp70 chaperones and their importance are conserved also in mammalian cells. Collectively, this study outlines a novel mechanism in the early events of the biogenesis of mitochondrial outer membrane β-barrel proteins.
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