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线粒体未折叠蛋白反应信号转导通路研究进展

马春伟^1,2, 高炳宏^3,*

¹上海体育学院运动科学学院，上海 200438；²运城学院体育系，运城 044000；³上海体育学院体育教育训练学院，上海 200438

摘要

线粒体未折叠蛋白反应是线粒体蛋白质质量控制程序的重要组成部分，在应激状态下可有效清除未折叠蛋白或错误折叠蛋白，维持线粒体池的稳定健康。线粒体未折叠蛋白反应由多条信号转导通路协调控制：经典的ATF4/ATF5-CHOP途径受线粒体基质中的未折叠蛋白或错误折叠蛋白积累诱发，通过调控分子伴侣和蛋白酶减轻应激毒性；Sirt3-FOXO3a-SOD2途径定位在线粒体基质中，在抗氧化损伤方面作用突出；ERα-NRF1-HTRA2途径主要清除线粒体膜间隙中的未折叠蛋白，提高线粒体蛋白质质量控制能力。这三条信号转导通路彼此独立，又存在交互作用，在机体应激状态下共同激发线粒体最大限度的适应能力，维护机体健康。

关键词： 线粒体未折叠蛋白反应; 信号转导通路; 交互作用

分类号：R318.4

Unfolded protein response signaling in mitochondria

MA Chun-Wei^1,2, GAO Bing-Hong^3,*

¹School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China；²Physical Education Department of Yuncheng University, Yuncheng 044000, China；³School of Physical Education and Sport Training, Shanghai University of Sport, Shanghai 200438, China

Abstract

The mitochondrial unfolded protein response is an important component of the mitochondrial protein quality control program. It can effectively remove unfolded or misfolded proteins under stress, and maintain a stable and healthy mitochondrial pool. The mitochondrial unfolded protein response is coordinated by multiple signaling pathways. The classical ATF4/ATF5-CHOP pathway is induced by accumulation of unfolded or misfolded proteins in the mitochondrial matrix, which reduces stress toxicity by regulating molecular chaperones and proteases. Sirt3-FOXO3a-SOD2 pathway, located in the mitochondrial matrix, plays an important role in anti-oxidative damage. The ERα-NRF1-HTRA2 pathway mainly removes unfolded proteins in the mitochondrial membrane space and improves the quality control of mitochondrial proteins. These three signaling pathways work both independently and cooperatively to enhance mitochondrial capacity and maintain health under stress.

Key words: mitochondrial unfolded protein response; signaling pathway; crosstalk

收稿日期：2020-09-02　　录用日期：2021-02-08

通讯作者：高炳宏　　E-mail: gaobinghong@126.com

DOI: 10.13294/j.aps.2021.0029

引用本文：

马春伟, 高炳宏. 线粒体未折叠蛋白反应信号转导通路研究进展[J]. 生理学报 2021; 73 (5): 835-844.

MA Chun-Wei, GAO Bing-Hong. Unfolded protein response signaling in mitochondria. Acta Physiol Sin 2021; 73 (5): 835-844 (in Chinese with English abstract).