Molecular genetic aspects of human mitochondrial disorders

This review focuses on mutations of mitochondrial DNA (mtDNA) which are an important cause of mitochondrial disorders in humans and are also associated with common neurodegenerative disorders and aging. The high copy number of mtDNA and its maternal transmission make the inheritance of mtDNA mutations fundamentally different from the Mendelian inheritance of nuclear DNA mutations. There is often a mixture of wild-type and mutated mtDNAs (heteroplasmy), and heterogeneity in the distribution of mutated mtDNAs is one plausible explanation for the widely varying phenotypes in patients with mitochondrial disorders. The application of molecular genetics has led to significant progress in the studies of human mitochondrial disorders in the past decade. Future studies including the development of animal models are needed to advance our understanding of the pathogenesis of mitochondrial disorders to enable, in turn, the development of novel therapies and genetic rescue strategies for the treatment of human disease.