蛋白酶体活性有助于对秀丽隐杆线虫轻度线粒体应激的促生存反应

Proteasome activity contributes to pro-survival response upon mild mitochondrial stress in Caenorhabditis elegans

Keywords：Defective mitochondrial function; protein defect; proteasome activation
关键词：线粒体功能缺陷；蛋白质缺陷；蛋白酶体激活

非哺乳动物：线虫
作者：Sladowska M, Turek M, Kim MJ, Drabikowski K, Mussulini BHM, Mohanraj K, Serwa RA, Topf U, Chacinska A 
出版期刊：《PLOS BIOLOGY》 2021/7/12

Abstract：

Defects in mitochondrial function activate compensatory responses in the cell. Mitochondrial stress that is caused by unfolded proteins inside the organelle induces a transcriptional response (termed the "mitochondrial unfolded protein response" [UPRmt]) that is mediated by activating transcription factor associated with stress 1 (ATFS-1). The UPRmt increases mitochondrial protein quality control. Mitochondrial dysfunction frequently causes defects in the import of proteins, resulting in the accumulation of mitochondrial proteins outside the organelle. In yeast, cells respond to mistargeted mitochondrial proteins by increasing activity of the proteasome in the cytosol (termed the "unfolded protein response activated by mistargeting of proteins" [UPRam]). The presence and relevance of this response in higher eukaryotes is unclear. Here, we demonstrate that defects in mitochondrial protein import in Caenorhabditis elegans lead to proteasome activation and life span extension. Both proteasome activation and life span prolongation partially depend on ATFS-1, despite its lack of influence on proteasomal gene transcription. Importantly, life span prolongation depends on the fully assembled proteasome. Our data provide a link between mitochondrial dysfunction and proteasomal activity and demonstrate its direct relevance to mechanisms that promote longevity.

文章摘要：

线粒体功能的缺陷会激活细胞中的代偿反应。由细胞器内未折叠蛋白引起的线粒体应激诱导转录反应（称为“线粒体未折叠蛋白反应”[UPRmt]），该反应由激活与应激相关的转录因子 1 (ATFS-1) 介导。 UPRmt 增加了线粒体蛋白质量控制。线粒体功能障碍经常导致蛋白质输入缺陷，导致线粒体蛋白质在细胞器外的积累。在酵母中，细胞通过增加胞质溶胶中蛋白酶体的活性来对错误靶向的线粒体蛋白做出反应（称为“由蛋白质错误靶向激活的未折叠蛋白质反应”[UPRam]）。这种反应在高等真核生物中的存在和相关性尚不清楚。在这里，我们证明了秀丽隐杆线虫中线粒体蛋白输入的缺陷导致蛋白酶体激活和寿命延长。蛋白酶体激活和寿命延长都部分依赖于 ATFS-1，尽管它对蛋白酶体基因转录缺乏影响。重要的是，寿命延长取决于完全组装的蛋白酶体。我们的数据提供了线粒体功能障碍和蛋白酶体活性之间的联系，并证明了它与促进长寿的机制直接相关。

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