David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2018 Apr 13;360(6385). doi: 10.1126/science.aan4146. Epub 2018 Apr 12.
Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Various disease and stress conditions can lead to mitochondrial import defects. We found that inhibition of mitochondrial import in budding yeast activated a surveillance mechanism, mitoCPR, that improved mitochondrial import and protected mitochondria during import stress. mitoCPR induced expression of Cis1, which associated with the mitochondrial translocase to reduce the accumulation of mitochondrial precursor proteins at the mitochondrial translocase. Clearance of precursor proteins depended on the Cis1-interacting AAA adenosine triphosphatase Msp1 and the proteasome, suggesting that Cis1 facilitates degradation of unimported proteins. mitoCPR was required for maintaining mitochondrial functions when protein import was compromised, demonstrating the importance of mitoCPR in protecting the mitochondrial compartment.
线粒体功能对于细胞存活至关重要，依赖于蛋白质向细胞器的输入。各种疾病和应激条件会导致线粒体输入缺陷。我们发现，在芽殖酵母中抑制线粒体输入会激活一种监控机制，mitoCPR，它可以改善线粒体输入，并在输入应激期间保护线粒体。mitoCPR 诱导 Cis1 的表达，它与线粒体转位酶结合，以减少线粒体前体蛋白在线粒体转位酶处的积累。前体蛋白的清除依赖于 Cis1 相互作用的 AAA 三磷酸腺苷酶 Msp1 和蛋白酶体，表明 Cis1 有助于未输入蛋白质的降解。当蛋白质输入受到损害时，mitoCPR 对于维持线粒体功能是必需的，这表明 mitoCPR 在保护线粒体区室方面的重要性。
