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.

破坏线粒体基因组的突变会导致许多人类疾病，这些人类疾病的表型表现在组织和个人之间差异很大。这种变异性部分归因于线粒体DNA（mtDNA）的非常规遗传学，包括多倍体，母体遗传和对核编码因子的依赖性。在果蝇中操纵线粒体基因组的遗传工具的最新发展，使这种功能强大的模型生物成为哺乳动物系统了解mtDNA相关疾病的诱人替代品。在这篇综述中，我们总结了mtDNA遗传学和人类mtDNA相关疾病。我们强调现有的果蝇mtDNA突变的模型，并讨论它们在增进我们对线粒体生物学知识和对人类线粒体疾病进行建模中的潜在用途。我们还讨论了基因治疗在mtDNA疾病未来治疗中的潜在和当前挑战。