Luo Hongke, Zhang Ruohan, Krigman Judith, McAdams Allison, Ozgen Serra, Sun Nuo
Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Front Cell Dev Biol. 2020 May 6;8:294. doi: 10.3389/fcell.2020.00294. eCollection 2020.
Mitochondrial dysfunction is a hallmark of aging and is a major contributor to neurodegenerative diseases and various cardiovascular disorders. Mitophagy, a specialized autophagic pathway to remove damaged mitochondria, provides a critical mechanism to maintain mitochondrial quality. This function has been implicated in a tissue's ability to appropriately respond to metabolic and to bioenergetic stress, as well as to recover from mitochondrial damage. A global decline in mitophagic flux has been postulated to be linked to pathological alterations that occur in the heart and the brain as well as a general age-dependent decline in organ function. Cellular observation suggests multiple mechanistically distinct pathways converge upon and activate mitophagy. Over the past decade, additional molecular components within mitophagy have been discovered, including several disease-associated genes that are functionally implicated in mitophagy. However, the pathophysiological role of mitophagy, and how it is regulated within normal physiology or various disease states, is less well established. Here, we will review the evidence that a decline in mitophagy contributes to impaired mitochondrial homeostasis and may be particularly detrimental to postmitotic neurons and cardiomyocytes. We will discuss mitophagy's pathological significance in both neurodegenerative diseases and cardiovascular disorders. Additionally, signaling pathways regulating mitophagy are reviewed, with emphasis placed on how these pathways might contribute to disease progression. Understanding mitophagy's role in the mechanisms of disease pathogenesis should allow for the development of more efficient strategies to battle pathological conditions associated with mitochondrial dysfunction.
线粒体功能障碍是衰老的一个标志，也是神经退行性疾病和各种心血管疾病的主要促成因素。线粒体自噬是一种清除受损线粒体的特殊自噬途径，是维持线粒体质量的关键机制。该功能与组织对代谢和生物能量应激做出适当反应以及从线粒体损伤中恢复的能力有关。据推测，线粒体自噬通量的整体下降与心脏和大脑中发生的病理改变以及器官功能普遍的年龄依赖性下降有关。细胞观察表明，多种机制不同的途径汇聚并激活线粒体自噬。在过去十年中，线粒体自噬中发现了更多的分子成分，包括几个在功能上与线粒体自噬相关的疾病相关基因。然而，线粒体自噬的病理生理作用以及它在正常生理或各种疾病状态下是如何被调节的，目前还不太清楚。在这里，我们将综述线粒体自噬下降导致线粒体稳态受损的证据，这可能对有丝分裂后神经元和心肌细胞特别有害。我们将讨论线粒体自噬在神经退行性疾病和心血管疾病中的病理意义。此外，还综述了调节线粒体自噬的信号通路，重点讨论了这些通路如何促进疾病进展。了解线粒体自噬在疾病发病机制中的作用，应该有助于开发更有效的策略来对抗与线粒体功能障碍相关的病理状况。
