mtDNA拷贝数的生物学意义及其调控

Biological Significances and Control of Mitochondrial DNA Copy Number

线粒体是细胞能量和自由基代谢中心,并在细胞凋亡、钙调控、细胞周期和信号转导中发挥重要作用,维持线粒体功能正常对于细胞正常行使职能意义重大。线粒体的功能与线粒体DNA(mitochondrial DNA,mtDNA)的数量和质量紧密相关,mtDNA的数量即mtDNA拷贝数又受到mtDNA质量的影响,因此mtDNA拷贝数可作为线粒体功能的重要表征。mtDNA拷贝数变异引起线粒体功能紊乱,进而导致疾病发生。本文综述了mtDNA拷贝数变异与神经退行性疾病、心血管疾病、肿瘤等疾病的发生发展和个体衰老之间的关系,以及mtDNA复制转录相关因子、氧化应激、细胞自噬等因素介导mtDNA拷贝数变异的调控机制。以期为进一步深入探究mtDNA拷贝数调控的分子机制,以及未来治疗神经退行性疾病、肿瘤及延缓衰老等提供一定的理论基础。

Mitochondria are the center of cellular energy and free radical metabolism,and it plays an important role in cell apoptosis,calcium regulation,cell cycle and signal transduction.Maintenance of mitochondrial function is significant for different types of cells to perform their normal functions.Mitochondrial function is strongly associated with the quantity and quality of mitochondrial DNA（mtDNA）,mtDNA amount which is known as mtDNA copy number is affected by the quality of mtDNA.mtDNA copy number is an important characterization of mitochondrial function.mtDNA copy number variation causes mitochondrial dysfunction,resulting in cellular function abnormity,eventually leading to the occurrence of various diseases.This review summarizes the correlation between mtDNA copy number variation and the development and advances of many diseases,such as neurodegenerative diseases,cardiovascular diseases,and cancer,as well as individual aging.In addition,it sums up the regulation mechanism of mtDNA copy number variation mediated by mtDNA replication transcription related factors,oxidative stress,and autophagy.This article will provide some theoretical basis to further explore the molecular mechanism of mtDNA copy number variation regulation,and provide new idea to develop potential treatment for neurodegenerative diseases,cardiovascular diseases,cancer and retardation of the aging process.