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线粒体质量监控:自噬在心血管健康和疾病中的作用。

Mitochondrial quality surveillance: mitophagy in cardiovascular health and disease.

机构信息

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California.

出版信息

Am J Physiol Cell Physiol. 2022 Feb 1;322(2):C218-C230. doi: 10.1152/ajpcell.00360.2021. Epub 2021 Dec 29.

Abstract

Selective autophagy of mitochondria, known as mitophagy, is a major quality control pathway in the heart that is involved in removing unwanted or dysfunctional mitochondria from the cell. Baseline mitophagy is critical for maintaining fitness of the mitochondrial network by continuous turnover of aged and less-functional mitochondria. Mitophagy is also critical in adapting to stress associated with mitochondrial damage or dysfunction. The removal of damaged mitochondria prevents reactive oxygen species-mediated damage to proteins and DNA and suppresses activation of inflammation and cell death. Impairments in mitophagy are associated with the pathogenesis of many diseases, including cancers, inflammatory diseases, neurodegeneration, and cardiovascular disease. Mitophagy is a highly regulated and complex process that requires the coordination of labeling dysfunctional mitochondria for degradation while simultaneously promoting de novo autophagosome biogenesis adjacent to the cargo. In this review, we provide an update on our current understanding of these steps in mitophagy induction and discuss the physiological and pathophysiological consequences of altered mitophagy in the heart.

摘要

线粒体的选择性自噬,称为线粒体自噬,是心脏中一种主要的质量控制途径,涉及从细胞中去除不需要的或功能失调的线粒体。基础线粒体自噬对于通过不断地更替老化和功能较低的线粒体来维持线粒体网络的适应性至关重要。线粒体自噬在适应与线粒体损伤或功能障碍相关的应激方面也很重要。清除受损的线粒体可以防止活性氧物质介导的蛋白质和 DNA 损伤,并抑制炎症和细胞死亡的激活。线粒体自噬的缺陷与许多疾病的发病机制有关,包括癌症、炎症性疾病、神经退行性疾病和心血管疾病。线粒体自噬是一个高度调控和复杂的过程,需要协调标记功能失调的线粒体进行降解,同时促进邻近货物的新自噬体生物发生。在这篇综述中,我们提供了对线粒体自噬诱导这些步骤的最新理解,并讨论了心脏中线粒体自噬改变的生理和病理生理后果。

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