Marín-García José
The Molecular Cardiology and Neuromuscular Institute, 75 Raritan Avenue, Highland Park, NJ, 08904, USA.
Heart Fail Rev. 2016 Sep;21(5):475-87. doi: 10.1007/s10741-016-9543-x.
Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS) and Ca(2+) handling to stress responses, cell survival and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular, cancer, premature aging and cardiovascular diseases (CVD), including myocardial ischemia, cardiomyopathy and heart failure (HF). Mitochondria contain their own genome organized into DNA-protein complexes, called "mitochondrial nucleoids," along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription and repair. Although the mammalian organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to various types of mtDNA damage. These include accumulation of mtDNA point mutations and/or deletions and decreased mtDNA copy number, which will impair mitochondrial function and finally, may lead to CVD including HF.
线粒体在各种细胞过程中发挥着关键作用，这些过程涵盖能量代谢、活性氧（ROS）生成、钙离子（Ca²⁺）处理，乃至应激反应、细胞存活与死亡。该细胞器功能异常可能导致神经肌肉疾病、癌症、早衰和心血管疾病（CVD），包括心肌缺血、心肌病和心力衰竭（HF）的发病机制。线粒体含有自身的基因组，该基因组组织成称为“线粒体核仁”的DNA - 蛋白质复合物，以及促进线粒体DNA（mtDNA）复制、转录和修复的多蛋白机制。尽管哺乳动物细胞器拥有几乎所有已知的核DNA修复途径，包括碱基切除修复、错配修复和重组修复，但mtDNA与ROS产生主要位点的接近以及缺乏保护性组蛋白，可能导致其对各种类型的mtDNA损伤敏感性增加。这些损伤包括mtDNA点突变和/或缺失的积累以及mtDNA拷贝数的减少，这将损害线粒体功能，最终可能导致包括HF在内的CVD。
