蛋白酶体损伤诱导线粒体膜电位恢复及线粒体融合的替代途径。
Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion.
作者信息
Shirozu Ryohei, Yashiroda Hideki, Murata Shigeo
机构信息
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
出版信息
Mol Cell Biol. 2015 Nov 9;36(2):347-62. doi: 10.1128/MCB.00920-15. Print 2016 Jan 15.
Mitochondria are vital and highly dynamic organelles that continuously fuse and divide to maintain mitochondrial quality. Mitochondrial dysfunction impairs cellular integrity and is known to be associated with various human diseases. However, the mechanism by which the quality of mitochondria is maintained remains largely unexplored. Here we show that impaired proteasome function recovers the growth of yeast cells lacking Fzo1, a pivotal protein for mitochondrial fusion. Decreased proteasome activity increased the mitochondrial oxidoreductase protein Mia40 and the ratio of the short isoform of mitochondrial intermembrane protein Mgm1 (s-Mgm1) to the long isoform (l-Mgm1). The increase in Mia40 restored mitochondrial membrane potential, while the increase in the s-Mgm1/l-Mgm1 ratio promoted mitochondrial fusion in an Fzo1-independent manner. Our findings demonstrate a new pathway for mitochondrial quality control that is induced by proteasome impairment.
线粒体是至关重要且高度动态的细胞器，它们持续融合与分裂以维持线粒体质量。线粒体功能障碍会损害细胞完整性，并且已知与多种人类疾病相关。然而，线粒体质量维持的机制在很大程度上仍未得到探索。在此我们表明，蛋白酶体功能受损可恢复缺乏Fzo1（线粒体融合的关键蛋白）的酵母细胞的生长。蛋白酶体活性降低会增加线粒体氧化还原酶蛋白Mia40以及线粒体内膜蛋白Mgm1的短异构体（s-Mgm1）与长异构体（l-Mgm1）的比例。Mia40的增加恢复了线粒体膜电位，而s-Mgm1/l-Mgm1比例的增加以不依赖Fzo1的方式促进了线粒体融合。我们的研究结果证明了一种由蛋白酶体损伤诱导的线粒体质量控制新途径。
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