National Heart, Lung and Blood Institute, National Institute of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
National Heart, Lung and Blood Institute, National Institute of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
J Genet Genomics. 2019 Apr 20;46(4):201-212. doi: 10.1016/j.jgg.2019.03.009. Epub 2019 Apr 23.
Mutations that disrupt the mitochondrial genome cause a number of human diseases whose phenotypic presentation varies widely among tissues and individuals. This variability owes in part to the unconventional genetics of mitochondrial DNA (mtDNA), which includes polyploidy, maternal inheritance and dependence on nuclear-encoded factors. The recent development of genetic tools for manipulating mitochondrial genome in Drosophila melanogaster renders this powerful model organism an attractive alternative to mammalian systems for understanding mtDNA-related diseases. In this review, we summarize mtDNA genetics and human mtDNA-related diseases. We highlight existing Drosophila models of mtDNA mutations and discuss their potential use in advancing our knowledge of mitochondrial biology and in modeling human mitochondrial disorders. We also discuss the potential and present challenges of gene therapy for the future treatment of mtDNA diseases.
线粒体基因组的突变会导致许多人类疾病，这些疾病在不同组织和个体中的表型表现差异很大。这种变异性部分归因于线粒体 DNA（mtDNA）的非常规遗传学，其中包括多倍体、母系遗传和对核编码因子的依赖。近年来，在黑腹果蝇中操纵线粒体基因组的遗传工具的发展，使得这种强大的模式生物成为哺乳动物系统的一个有吸引力的替代品，用于理解与 mtDNA 相关的疾病。在这篇综述中，我们总结了 mtDNA 遗传学和人类 mtDNA 相关疾病。我们强调了现有的果蝇 mtDNA 突变模型，并讨论了它们在推进线粒体生物学知识和模拟人类线粒体疾病方面的潜在用途。我们还讨论了基因治疗的潜力和当前挑战，以及未来治疗 mtDNA 疾病的前景。
