Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia.
Cells. 2021 Dec 23;11(1):38. doi: 10.3390/cells11010038.
Mitochondria in the cell are the center for energy production, essential biomolecule synthesis, and cell fate determination. Moreover, the mitochondrial functional versatility enables cells to adapt to the changes in cellular environment and various stresses. In the process of discharging its cellular duties, mitochondria face multiple types of challenges, such as oxidative stress, protein-related challenges (import, folding, and degradation) and mitochondrial DNA damage. They mitigate all these challenges with robust quality control mechanisms which include antioxidant defenses, proteostasis systems (chaperones and proteases) and mitochondrial biogenesis. Failure of these quality control mechanisms leaves mitochondria as terminally damaged, which then have to be promptly cleared from the cells before they become a threat to cell survival. Such damaged mitochondria are degraded by a selective form of autophagy called mitophagy. Rigorous research in the field has identified multiple types of mitophagy processes based on targeting signals on damaged or superfluous mitochondria. In this review, we provide an in-depth overview of mammalian mitophagy and its importance in human health and diseases. We also attempted to highlight the future area of investigation in the field of mitophagy.
细胞中的线粒体是能量产生、重要生物分子合成和细胞命运决定的中心。此外，线粒体功能的多功能性使细胞能够适应细胞环境和各种应激的变化。在履行其细胞职责的过程中，线粒体面临多种类型的挑战，如氧化应激、与蛋白质相关的挑战（输入、折叠和降解）和线粒体 DNA 损伤。它们通过强大的质量控制机制来减轻所有这些挑战，包括抗氧化防御、蛋白质稳定系统（伴侣蛋白和蛋白酶）和线粒体生物发生。如果这些质量控制机制失效，线粒体就会受到终末损伤，然后必须在它们对细胞存活造成威胁之前从细胞中迅速清除。这种受损的线粒体通过一种称为自噬的选择性自噬形式被降解。该领域的严格研究根据损伤或多余线粒体上的靶向信号，确定了多种类型的自噬过程。在这篇综述中，我们深入概述了哺乳动物的自噬及其在人类健康和疾病中的重要性。我们还试图强调自噬领域未来的研究领域。
