亮氨酰-tRNA合成酶在調(diào)控衰老骨骼肌蛋白質(zhì)合成中的作用與機制
夏志1, 尚畫雨2, 王前進1, 趙艷1, 丁孝民1,*
1井岡山大學體育學院，吉安 343009；2成都體育學院運動醫(yī)學與健康學院，成都 610041
摘要
蛋白質(zhì)代謝平衡紊亂是誘發(fā)骨骼肌萎縮的根本原因，蛋白質(zhì)合成減少則直接導致衰老性骨骼肌萎縮的發(fā)生與發(fā)展。亮氨酰-tRNA合成酶(leucyl-tRNA synthetase, LeuRS)的經(jīng)典功能是催化亮氨酸與其同工tRNA之間連接形成氨基酰，在生物體內(nèi)遺傳解碼過程中具有重要作用。隨著近年對LeuRS蛋白研究的深入，人們認為其可能通過行使非經(jīng)典功能而在衰老骨骼肌蛋白質(zhì)代謝穩(wěn)態(tài)調(diào)節(jié)中發(fā)揮關鍵作用。本文綜述了氨基酰-tRNA合成酶和LeuRS的結(jié)構(gòu)與生物學特性，并重點對LeuRS作為細胞內(nèi)亮氨酸傳感器調(diào)控衰老骨骼肌細胞蛋白質(zhì)合成的研究進展進行總結(jié)，分析了LeuRS響應運動與氨基酸攝入等合成代謝刺激，活化哺乳動物雷帕霉素靶蛋白復合物1 (mammalian target of rapamycin complex 1, mTORC1)信號轉(zhuǎn)導通路的作用機制，以期為衰老性骨骼肌萎縮的預防和診治提供新的思路。
關鍵詞： 亮氨酰-tRNA合成酶; 衰老; 骨骼肌蛋白質(zhì)合成; 衰老性骨骼肌萎縮; 雷帕霉素靶蛋白復合物1
分類號：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-Min1,*
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　　錄用日期：2019-12-26
通訊作者：丁孝民　　E-mail: dingxiaomin@126.com
DOI: 10.13294/j.aps.2020.0053
引用本文：
夏志, 尚畫雨, 王前進, 趙艷, 丁孝民. 亮氨酰-tRNA合成酶在調(diào)控衰老骨骼肌蛋白質(zhì)合成中的作用與機制[J]. 生理學報 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).

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