Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
Antioxid Redox Signal. 2021 Mar 1;34(7):517-530. doi: 10.1089/ars.2020.8058. Epub 2020 Apr 7.
Mitochondria represent a major source of intracellular reactive oxygen species (ROS) generation. This is often a consequence of oxidative phosphorylation, which can produce ROS as a result of leakage from the electron transport chain. In addition, quality control mechanisms exist to protect cells from cytotoxic ROS production. One such mechanism is selective autophagic degradation of ROS-producing mitochondria, termed mitophagy, that ultimately results in elimination of mitochondria in the lysosome. However, while the relationship between mitophagy and ROS production is clearly interwoven, it is yet to be fully untangled. In some circumstances, mitochondrial ROS (mtROS) are elevated as a consequence of mitophagy induction. In this review, we discuss mtROS generation and their detrimental effects on cellular viability. In addition, we consider the cellular defense mechanisms that the eukaryotic cell uses to abrogate superfluous oxidative stress. In particular, we delve into the prominent mechanisms governing mitophagy induction that bear on oxidative stress. Finally, we examine the pathological conditions associated with defective mitophagy, where additional research may help to facilitate understanding.
线粒体是细胞内活性氧（ROS）产生的主要来源。这通常是氧化磷酸化的结果，电子传递链的泄漏会导致 ROS 的产生。此外，还存在质量控制机制来保护细胞免受细胞毒性 ROS 的产生。一种这样的机制是选择性自噬降解产生 ROS 的线粒体，称为线粒体自噬，最终导致溶酶体中线粒体的消除。然而，虽然线粒体自噬和 ROS 产生之间的关系显然交织在一起，但尚未完全理清。在某些情况下，线粒体 ROS（mtROS）的升高是由于线粒体自噬的诱导。在这篇综述中，我们讨论了 mtROS 的产生及其对细胞活力的有害影响。此外，我们还考虑了真核细胞用来消除多余氧化应激的细胞防御机制。特别是，我们深入研究了控制线粒体自噬诱导的主要机制，这些机制与氧化应激有关。最后，我们研究了与线粒体自噬缺陷相关的病理状况，在这些状况下，进一步的研究可能有助于促进理解。
