Hu Shengnan, Tang Xueying, Zhu Fangrui, Liang Chen, Wang Sa, Wang Hongjie, Li Peifeng, Li Yuzhen
School of Basic Medical Sciences, Hebei University, Baoding, Hebei 071002, China.
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
Genes Dis. 2024 Mar 28;12(3):101282. doi: 10.1016/j.gendis.2024.101282. eCollection 2025 May.
Mitochondria serve as the energy provider and enable life activities, and they are the only organelles containing extra-chromosomal DNA. Each mitochondrion contains multiple copies of its genome, which is usually referred to as mitochondrial DNA (mtDNA). mtDNA encodes necessary electron transport chain complex subunits, as well as the essential RNAs for their translation within the organelle. Therefore, the precondition for intact mitochondrial function and cardiomyocyte survival is the integrity of mtDNA. Accumulating evidence suggests that the disruption of mtDNA integrity is involved in ischemia/reperfusion-induced mitochondrial dysfunction and cardiomyocyte injury. Here, we review the current opinions about the pathways of mtDNA integrity maintenance and discuss the role of mtDNA integrity in cardiomyocyte injury reacting to ischemia/reperfusion. We also discuss the mechanisms by which mtDNA mediates ischemia/reperfusion-induced cardiomyocyte injury, together with therapeutic strategies by targeting mtDNA.
线粒体作为能量提供者,维持生命活动,且是唯一含有染色体外DNA的细胞器。每个线粒体都包含其基因组的多个拷贝,该基因组通常被称为线粒体DNA(mtDNA)。mtDNA编码电子传递链复合物的必要亚基,以及在线粒体内进行翻译所需的RNA。因此,线粒体功能完整和心肌细胞存活的前提是mtDNA的完整性。越来越多的证据表明,mtDNA完整性的破坏与缺血/再灌注诱导的线粒体功能障碍和心肌细胞损伤有关。在此,我们综述了目前关于mtDNA完整性维持途径的观点,并讨论了mtDNA完整性在心肌细胞对缺血/再灌注损伤反应中的作用。我们还讨论了mtDNA介导缺血/再灌注诱导的心肌细胞损伤的机制,以及针对mtDNA的治疗策略。