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亮氨酰-tRNA合成酶在调控衰老骨骼肌蛋白质合成中的作用与机制

夏志¹, 尚画雨², 王前进¹, 赵艳¹, 丁孝民^1,*

¹井冈山大学体育学院，吉安 343009；²成都体育学院运动医学与健康学院，成都 610041

摘要

蛋白质代谢平衡紊乱是诱发骨骼肌萎缩的根本原因，蛋白质合成减少则直接导致衰老性骨骼肌萎缩的发生与发展。亮氨酰-tRNA合成酶(leucyl-tRNA synthetase, LeuRS)的经典功能是催化亮氨酸与其同工tRNA之间连接形成氨基酰，在生物体内遗传解码过程中具有重要作用。随着近年对LeuRS蛋白研究的深入，人们认为其可能通过行使非经典功能而在衰老骨骼肌蛋白质代谢稳态调节中发挥关键作用。本文综述了氨基酰-tRNA合成酶和LeuRS的结构与生物学特性，并重点对LeuRS作为细胞内亮氨酸传感器调控衰老骨骼肌细胞蛋白质合成的研究进展进行总结，分析了LeuRS响应运动与氨基酸摄入等合成代谢刺激，活化哺乳动物雷帕霉素靶蛋白复合物1 (mammalian target of rapamycin complex 1, mTORC1)信号转导通路的作用机制，以期为衰老性骨骼肌萎缩的预防和诊治提供新的思路。

关键词： 亮氨酰-tRNA合成酶; 衰老; 骨骼肌蛋白质合成; 衰老性骨骼肌萎缩; 雷帕霉素靶蛋白复合物1

分类号：R3; Q4; Q5

The role and mechanism of leucyl-tRNA synthetase in the regulation of protein synthesis in aging skeletal muscle

XIA Zhi¹, SHANG Hua-Yu², WANG Qian-Jin¹, ZHAO Yan¹, DING Xiao-Min^1,*

¹College of Physical Education, Jinggangshan University, Ji’an 343009, China；²School of Sports Medicine and Health, Chengdu Sport Institute, Chengdu 610041, China

Abstract

The imbalance of protein metabolism is the major cause of skeletal muscle atrophy, and the decrease of protein synthesis directly leads to the occurrence and development of age-related sarcopenia. The canonical role of leucyl-tRNA synthetase (LeuRS) is ligating leucine to the cognate tRNA, and thus it plays a central role in genetic coding. With the further studies of LeuRS in recent years, LeuRS has been found to control protein homeostasis in aging skeletal muscle via its non-canonical role. In this paper, we reviewed the structure and biological features of aminoacyl-tRNA synthetase and LeuRS, and summarized the recent advances in studies on the effects of LeuRS in regulating aging skeletal muscle protein synthesis as an intracellular leucine sensor. Moreover, we also analyzed the potential role of LeuRS in activation of mammalian target of rapamycin complex 1 (mTORC1) signaling transduction pathway in response to anabolic stimuli such as exercise and amino acids ingestion. This paper may provide some new ideas for the prevention, diagnosis and treatment of age-related sarcopenia.

Key words: leucyl-tRNA synthetase; aging; skeletal muscle protein synthesis; age-related sarcopenia; target of rapamycin complex 1

收稿日期：2019-09-22　　录用日期：2019-12-26

通讯作者：丁孝民　　E-mail: dingxiaomin@126.com

DOI: 10.13294/j.aps.2020.0053

引用本文：

夏志, 尚画雨, 王前进, 赵艳, 丁孝民. 亮氨酰-tRNA合成酶在调控衰老骨骼肌蛋白质合成中的作用与机制[J]. 生理学报 2020; 72 (4): 523-531.

XIA Zhi, SHANG Hua-Yu, WANG Qian-Jin, ZHAO Yan, DING Xiao-Min. The role and mechanism of leucyl-tRNA synthetase in the regulation of protein synthesis in aging skeletal muscle. Acta Physiol Sin 2020; 72 (4): 523-531 (in Chinese with English abstract).