MITOCHONDRIAL DNA MUTATIONS IN HUMAN DISEASE

Abstract | The human mitochondrial genome is extremely small compared with the nuclear genome, and mitochondrial genetics presents unique clinical and experimental challenges. Despite the diminutive size of the mitochondrial genome, mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease. Recent years have witnessed considerable progress in understanding basic mitochondrial genetics and the relationship between inherited mutations and disease phenotypes, and in identifying acquired mtDNA mutations in both ageing and cancer. However, many challenges remain, including the prevention and treatment of these diseases. This review explores the advances that have been made and the areas in which future progress is likely. Until recently, mitochondrial genetics and diseases that are due to defects in mitochondrial DNA (mtDNA) were often considered to be curiosities, outside main-stream genetics. These views were not helped by the different genetic rules by which mtDNA is inherited compared with nuclear DNA, the presence of sev-eral mtDNA copies in individual cells and a belie