Jiang Jingwen, Peng Liyuan, Wang Kui, Huang Canhua
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
Antioxid Redox Signal. 2021 May 1;34(13):979-1003. doi: 10.1089/ars.2020.8123. Epub 2020 Jul 30.
Metabolic reprogramming is considered to be a critical adaptive biological event that fulfills the energy and biomass demands for cancer cells. One hallmark of metabolic reprogramming is reduced oxidative phosphorylation and enhanced aerobic glycolysis. Such metabolic abnormalities contribute to the accumulation of reactive oxygen species (ROS), the by-products of metabolic pathways. Emerging evidence suggests that ROS can in turn directly or indirectly affect the expression, activity, or subcellular localization of metabolic enzymes, contributing to the moonlighting functions outside of their primary roles. This review summarizes the multifunctions of metabolic enzymes and the involved redox modification patterns, which further reveal the inherent connection between metabolism and cellular redox state. These noncanonical functions of metabolic enzymes involve the regulation of epigenetic modifications, gene transcription, post-translational modification, cellular antioxidant capacity, and many other fundamental cellular events. The multifunctional properties of metabolic enzymes further expand the metabolic dependencies of cancer cells, and confer cancer cells with a means of adapting to diverse environmental stimuli. Deciphering the redox-manipulated mechanisms with specific emphasis on the moonlighting function of metabolic enzymes is important for clarifying the pertinence between metabolism and redox processes. Investigation of the redox-regulated moonlighting functions of metabolic enzymes will shed new lights into the mechanism by which metabolic enzymes gain noncanonical functions, and yield new insights into the development of novel therapeutic strategies for cancer treatment by targeting metabolic-redox abnormalities. 34, 979-1003.
代谢重编程被认为是一种关键的适应性生物学事件，可满足癌细胞对能量和生物量的需求。代谢重编程的一个标志是氧化磷酸化减少和有氧糖酵解增强。这种代谢异常会导致活性氧（ROS）的积累，ROS是代谢途径的副产物。新出现的证据表明，ROS反过来可以直接或间接影响代谢酶的表达、活性或亚细胞定位，从而导致其在主要功能之外的兼职功能。本综述总结了代谢酶的多种功能以及所涉及的氧化还原修饰模式，进一步揭示了代谢与细胞氧化还原状态之间的内在联系。代谢酶的这些非经典功能涉及表观遗传修饰、基因转录、翻译后修饰、细胞抗氧化能力以及许多其他基本细胞事件的调节。代谢酶的多功能特性进一步扩展了癌细胞的代谢依赖性，并赋予癌细胞适应多种环境刺激的手段。阐明氧化还原操纵机制，特别强调代谢酶的兼职功能，对于阐明代谢与氧化还原过程之间的相关性很重要。研究代谢酶的氧化还原调节兼职功能将为代谢酶获得非经典功能的机制提供新的线索，并为通过靶向代谢 - 氧化还原异常开发新的癌症治疗策略提供新的见解。34, 979 - 1003。
