Pex19 is involved in importing dually targeted tail-anchored proteins to both mitochondria and peroxisomes
Pex19 is involved in importing dually targeted tail-anchored proteins to both mitochondria and peroxisomes
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DOI：
10.1111/tra.12604
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发表时间：
2018-10-01
期刊：
影响因子：
4.5
通讯作者：
Rapaport, Doron
中科院分区：
文献类型：
--
作者：
Cichocki, Bogdan A.;Krumpe, Katrin;Rapaport, Doron
尾部锚定(Tail-Anchored，TA)蛋白通过其C末端的一个跨膜片段嵌入到相应的膜中，而大部分蛋白面向胞浆。到目前为止，还没有发现介导这些蛋白质整合到线粒体外膜的细胞因素。以发芽酵母为模型系统，我们确定胞质Hsp70分子伴侣Ssa1和过氧化物体输入因子Pex19是线粒体TA蛋白亚群的重要介体。因此，PEX19的缺失导致：(1)呼吸条件下的生长缺陷，(2)线粒体形态的改变，(3)线粒体TA蛋白Fis1和Gem1的稳定水平降低，以及(4)TA蛋白Fis1和Gem1的细胞器输入受阻。此外，重组Pex19可以直接与TA蛋白Fis1和Gem1结合。总的来说，这项工作确定了参与线粒体TA蛋白生物发生的第一批因素，并揭示了Pex19意想不到的功能。
Tail-anchored (TA) proteins are embedded into their corresponding membrane via a single transmembrane segment at their C-terminus whereas the majority of the protein is facing the cytosol. So far, cellular factors that mediate the integration of such proteins into the mitochondrial outer membrane were not found. Using budding yeast as a model system, we identified the cytosolic Hsp70 chaperone Ssa1 and the peroxisome import factor Pex19 as import mediators for a subset of mitochondrial TA proteins. Accordingly, deletion of PEX19 results in: (1) growth defect under respiration conditions, (2) alteration in mitochondrial morphology, (3) reduced steady-state levels of the mitochondrial TA proteins Fis1 and Gem1, and (4) hampered in organello import of the TA proteins Fis1 and Gem1. Furthermore, recombinant Pex19 can bind directly the TA proteins Fis1 and Gem1. Collectively, this work identified the first factors that are involved in the biogenesis of mitochondrial TA proteins and uncovered an unexpected function of Pex19.