跨组织线粒体应激信号交流调控机体衰老研究进展
收稿日期: 2022-12-21
修回日期: 2023-01-30
网络出版日期: 2023-02-24
基金资助
国家自然科学基金项目(32200624);，博士后创新人才支持计划(BX2021356);博士后面上项目(2021M703474)
Inter-tissue communication of mitochondrial stress in aging
Received date: 2022-12-21
Revised date: 2023-01-30
Online published: 2023-02-24
Supported by
the National Natural Science Foundation of China(32200624);the China National Postdoctoral Program for Innovative Talents(BX2021356);the China Postdoctoral Science Foundation Funded Project(2021M703474)
线粒体内蛋白质稳态的平衡对于细胞正常的生理功能非常关键。线粒体蛋白稳态失衡时，细胞会启动应激反应机制，即线粒体未折叠蛋白反应(mitochondrial unfolded protein response，UPRmt)，修复线粒体功能，平衡细胞内稳态。尽管线粒体的严重损伤对机体是有害的，但在线虫(Caenorhabditis elegans)、果蝇(Drosophila melanogaste)及小鼠(Mus musculus)中都有研究表明线粒体的轻微损伤可以通过激活UPRmt，促进寿命延长。有趣的是，在没有直接经历线粒体损伤的细胞或组织中，UPRmt也能以非自主方式被诱导。不同组织间可以通过名为“mitokine”的细胞因子进行UPRmt的跨组织调控，系统性地协调机体整体的压力适应能力和抗衰老能力。该调控机制与衰老相关神经退行性疾病、癌症等多种疾病密切相关，近年来有关研究与日俱增。本文系统总结了线粒体应激及其组织间通讯的机制，并介绍了跨组织线粒体应激交流信号“mitokine”调控衰老进程的最新研究进展，以期为跨组织信号调控和机体衰老等研究提供参考。
关键词： 线粒体未折叠蛋白反应; 蛋白稳态; 跨组织调控; 衰老
张茜, 王子豪, 田烨 . 跨组织线粒体应激信号交流调控机体衰老研究进展[J]. 遗传, 2023 , 45(3) : 187 -197 . DOI: 10.16288/j.yczz.22-416
The protein homeostasis in mitochondria is critical for the normal physiological function of cells. To cope with mitochondrial stress, cells elicit specific stress response named mitochondrial unfolded protein response (UPRmt), to maintain mitochondrial homeostasis and repair mitochondrial function. Although severe damage to mitochondria is detrimental, studies in worms, flies, and mice have shown that mild mitochondrial damage promotes longevity by activating UPRmt. Interestingly, UPRmt can also be induced in a cell non-autonomous manner in cells or tissues which are not directly experiencing mitochondrial stress. The secreted molecules called “mitokine” are responsible for the mitochondrial stress communication between different tissues. This inter-tissue regulation of mitochondrial stress response systematically coordinates the adaptation ability which is closely associated with aging and a variety of diseases such as neurodegeneration and cancer. In this review, we summarize recent advances about inter-tissue mitochondrial stress communications, and introduce the current knowledge about the “mitokine” and its regulation on aging for further studies.
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