Zhou Hao, Ren Jun, Toan Sam, Mui David
Department of Cardiology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Ageing Res Rev. 2021 Mar;66:101250. doi: 10.1016/j.arr.2020.101250. Epub 2020 Dec 31.
Myocardial infarction (MI) is the irreversible death of cardiomyocyte secondary to prolonged lack of oxygen or fresh blood supply. Historically considered as merely cardiomyocyte powerhouse that manufactures ATP and other metabolites, mitochondrion is recently being identified as a signal regulator that is implicated in the crosstalk and signal integration of cardiomyocyte contraction, metabolism, inflammation, and death. Mitochondria quality surveillance is an integrated network system modifying mitochondrial structure and function through the coordination of various processes including mitochondrial fission, fusion, biogenesis, bioenergetics, proteostasis, and degradation via mitophagy. Mitochondrial fission favors the elimination of depolarized mitochondria through mitophagy, whereas mitochondrial fusion preserves the mitochondrial network upon stress through integration of two or more small mitochondria into an interconnected phenotype. Mitochondrial biogenesis represents a regenerative program to replace old and damaged mitochondria with new and healthy ones. Mitochondrial bioenergetics is regulated by a metabolic switch between glucose and fatty acid usage, depending on oxygen availability. To maintain the diversity and function of mitochondrial proteins, a specialized protein quality control machinery regulates protein dynamics and function through the activity of chaperones and proteases, and induction of the mitochondrial unfolded protein response. In this review, we provide an overview of the molecular mechanisms governing mitochondrial quality surveillance and highlight the most recent preclinical and clinical therapeutic approaches to restore mitochondrial fitness during both MI and post-MI heart failure.
心肌梗死（MI）是由于长期缺氧或缺乏新鲜血液供应导致的心肌细胞不可逆死亡。线粒体在历史上仅被视为制造ATP和其他代谢产物的心肌细胞动力源，但最近它被确定为一种信号调节因子，参与心肌细胞收缩、代谢、炎症和死亡的相互作用及信号整合。线粒体质量监测是一个综合网络系统，通过协调包括线粒体分裂、融合、生物发生、生物能量学、蛋白质稳态以及通过线粒体自噬进行降解等各种过程来改变线粒体的结构和功能。线粒体分裂有利于通过线粒体自噬消除去极化的线粒体，而线粒体融合则通过将两个或更多个小线粒体整合为相互连接的表型来在应激时维持线粒体网络。线粒体生物发生是一个再生程序，用新的健康线粒体替代旧的和受损的线粒体。线粒体生物能量学受葡萄糖和脂肪酸利用之间的代谢转换调节，这取决于氧气的可用性。为了维持线粒体蛋白质的多样性和功能，一种专门的蛋白质质量控制机制通过伴侣蛋白和蛋白酶的活性以及诱导线粒体未折叠蛋白反应来调节蛋白质动力学和功能。在本综述中，我们概述了控制线粒体质量监测的分子机制，并强调了在心肌梗死和心肌梗死后心力衰竭期间恢复线粒体健康的最新临床前和临床治疗方法。
