Department of Pathology and Genomic Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia 19107, United States.
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, 199 Renai Road, Suzhou 215123, China.
Hum Mol Genet. 2024 May 22;33(R1):R12-R18. doi: 10.1093/hmg/ddae048.
Mitochondria are subcellular organelles essential for life. Beyond their role in producing energy, mitochondria govern various physiological mechanisms, encompassing energy generation, metabolic processes, apoptotic events, and immune responses. Mitochondria also contain genetic material that is susceptible to various forms of damage. Mitochondrial double-stranded breaks (DSB) are toxic lesions that the nucleus repairs promptly. Nevertheless, the significance of DSB repair in mammalian mitochondria is controversial. This review presents an updated view of the available research on the consequences of mitochondrial DNA DSB from the molecular to the cellular level. We discuss the crucial function of mitochondrial DNA damage in regulating processes such as senescence, integrated stress response, and innate immunity. Lastly, we discuss the potential role of mitochondrial DNA DSB in mediating the cellular consequences of ionizing radiations, the standard of care in treating solid tumors.
线粒体是细胞内的细胞器，对生命至关重要。除了产生能量的作用外，线粒体还调控着各种生理机制，包括能量生成、代谢过程、细胞凋亡和免疫反应。线粒体还含有易受各种形式损伤的遗传物质。线粒体双链断裂（DSB）是一种毒性损伤，细胞核会迅速修复。然而，哺乳动物线粒体中 DSB 修复的意义仍存在争议。本综述从分子到细胞水平，呈现了线粒体 DNA DSB 后果的现有研究的最新观点。我们讨论了线粒体 DNA 损伤在调节衰老、整合应激反应和先天免疫等过程中的关键功能。最后，我们讨论了线粒体 DNA DSB 在介导电离辐射的细胞后果方面的潜在作用，电离辐射是治疗实体瘤的标准治疗方法。
