The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology
The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology
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DOI：
10.1111/febs.13813
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发表时间：
2016-09-01
期刊：
影响因子：
5.4
通讯作者：
Rapaport, Doron
中科院分区：
文献类型：
--
作者：
Hoseini, Hoda;Pandey, Saroj;Rapaport, Doron
大多数线粒体蛋白质在进入细胞器之前在胞质溶胶中合成。人们普遍认为，胞质因子是将前体蛋白质递送到线粒体表面和保持新合成的蛋白质处于可输入构象所必需的。然而，这些因素的身份及其对进口过程的明确贡献大多是未知的。使用前序列包含的模型蛋白质和酵母细胞中的定点光交联方法，我们确定了胞质分子伴侣Hsp70（Ssa1）和Hsp90（Hsp82）以及它们的cochaperones，Sti1和Ydj1，作为假定的参与线粒体蛋白质进口的胞质因子。STI1的缺失导致线粒体形态的改变和线粒体蛋白亚组的稳态水平降低。此外，STI1与线粒体输入因子MIM1或TOM 20的双缺失显示出合成生长表型，表明STI1与这些基因的遗传相互作用。此外，输入受体Tom20和Tom70的重组胞质结构域能够在体外结合Sti1和其他胞质因子。总之，我们的观察指出，直接或间接，作用的Sti1线粒体功能。
Most mitochondrial proteins are synthesized in the cytosol prior to their import into the organelle. It is commonly accepted that cytosolic factors are required for delivering precursor proteins to the mitochondrial surface and for keeping newly synthesized proteins in an import-competent conformation. However, the identity of such factors and their defined contribution to the import process are mostly unknown. Using a presequence-containing model protein and a site-directed photo-crosslinking approach in yeast cells we identified the cytosolic chaperones Hsp70 (Ssa1) and Hsp90 (Hsp82) as well as their cochaperones, Sti1 and Ydj1, as putative cytosolic factors involved in mitochondrial protein import. Deletion of STI1 caused both alterations in mitochondrial morphology and lower steady-state levels of a subset of mitochondrial proteins. In addition, double deletion of STI1 with the mitochondrial import factors, MIM1 or TOM20, showed a synthetic growth phenotype indicating a genetic interaction of STI1 with these genes. Moreover, recombinant cytosolic domains of the import receptors Tom20 and Tom70 were able to bind in vitro Sti1 and other cytosolic factors. In summary, our observations point to a, direct or indirect, role of Sti1 for mitochondrial functionality.