摘要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.