Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
Biochim Biophys Acta Mol Cell Res. 2022 May;1869(5):119233. doi: 10.1016/j.bbamcr.2022.119233. Epub 2022 Feb 5.
Mitochondrion is a double membrane organelle that is responsible for cellular respiration and production of most of the ATP in eukaryotic cells. Mitochondrial DNA (mtDNA) is the genetic material carried by mitochondria, which encodes some essential subunits of respiratory complexes independent of nuclear DNA. Normally, mtDNA binds to certain proteins to form a nucleoid that is stable in mitochondria. Nevertheless, a variety of physiological or pathological stresses can cause mtDNA damage, and the accumulation of damaged mtDNA in mitochondria leads to mitochondrial dysfunction, which triggers the occurrence of mitochondrial diseases in vivo. In response to mtDNA damage, cell initiates multiple pathways including mtDNA repair, degradation, clearance and release, to recover mtDNA, and maintain mitochondrial quality and cell homeostasis. In this review, we provide our current understanding of the fate of damaged mtDNA, focus on the pathways and mechanisms of removing damaged mtDNA in the cell.
线粒体是一种双层膜细胞器，负责真核细胞的呼吸作用和大部分 ATP 的生成。线粒体 DNA（mtDNA）是线粒体携带的遗传物质，它独立于核 DNA 编码呼吸复合物的一些必需亚基。正常情况下，mtDNA 与某些蛋白质结合形成在线粒体中稳定的核体。然而，各种生理或病理应激可导致 mtDNA 损伤，线粒体中受损 mtDNA 的积累导致线粒体功能障碍，从而引发体内线粒体疾病的发生。为了应对 mtDNA 损伤，细胞会启动多种途径，包括 mtDNA 修复、降解、清除和释放，以恢复 mtDNA，维持线粒体质量和细胞内稳态。在这篇综述中，我们提供了对受损 mtDNA 命运的最新理解，重点介绍了细胞内清除受损 mtDNA 的途径和机制。
