MOLECULAR-GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS

This review focuses on mutations of mitochondrial DNA (mtDNA) which ar e an important cause of mitochondrial disorders in humans and are also associated with common neurodegenerative disorders and aging. The hig h copy number of mtDNA and its maternal transmission make the inherita nce of mtDNA mutations fundamentally different from the Mendelian inhe ritance of nuclear DNA mutations. There is often a mixture of wild-typ e and mutated mtDNAs (heteroplasmy), and heterogeneity in the distribu tion of mutated mtDNAs is one plausible explanation for the widely var ying phenotypes in patients with mitochondrial disorders. The applicat ion of molecular genetics has led to significant progress in the studi es 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 strat egies for the treatment of human disease.