Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion
Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion
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DOI：
10.1128/mcb.00920-15
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发表时间：
2015-11
影响因子：
5.3
通讯作者：
Ryohei Shirozu;H. Yashiroda;S. Murata
中科院分区：
文献类型：
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作者：
Ryohei Shirozu;H. Yashiroda;S. Murata
摘要线粒体是一种重要的、高度动态的细胞器，通过不断的融合和分裂来维持线粒体的质量。线粒体功能障碍损害细胞完整性，并且已知与各种人类疾病相关。然而，维持线粒体质量的机制在很大程度上仍未被探索。在这里，我们表明，受损的蛋白酶体功能恢复缺乏Fzo 1，线粒体融合的关键蛋白质的酵母细胞的生长。降低蛋白酶体活性增加了线粒体氧化还原酶蛋白Mia 40和线粒体膜间蛋白Mgm 1（s-Mgm 1）的短亚型长亚型（l-Mgm 1）的比例。Mia 40的增加恢复了线粒体膜电位，而s-Mgm 1/l-Mgm 1比率的增加以Fzo 1非依赖的方式促进了线粒体融合。我们的研究结果证明了一种新的线粒体质量控制途径，是由蛋白酶体损伤引起的。
ABSTRACT 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.