Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Center for Integrated Protein Science, Department Chemie, Technische Universität München, Garching, Germany.
J Cell Biol. 2018 Sep 3;217(9):3091-3108. doi: 10.1083/jcb.201712029. Epub 2018 Jun 21.
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.
线粒体β-桶状蛋白由核编码，在细胞质核糖体上翻译，然后导入细胞器。最近，人们对β-桶状蛋白的线粒体内部导入途径有了详细的了解。相比之下，新合成的β-桶状蛋白如何以具有导入能力的构象到达线粒体表面仍然完全不清楚。在这项研究中，我们表明细胞质热休克蛋白 70（Hsp70）伴侣及其 Hsp40 共伴侣 Ydj1 和 Sis1 与新合成的β-桶状蛋白相互作用。这些相互作用对于正确的生物发生至关重要，因为抑制细胞质 Hsp70 的活性、阻止其与线粒体受体 Tom70 对接，或耗尽 Ydj1 和 Sis1，都会导致这些底物向线粒体的导入显著减少。进一步的实验表明，β-桶状蛋白与 Hsp70 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-桶状蛋白生物发生早期事件的一种新机制。
