Human mitochondrial DNA: roles of inherited and somatic mutations

This Review discusses the roles of mitochondrial DNA (mtDNA) mutations in human disease. In addition to many primary mitochondrial diseases, there is emerging — and sometimes controversial — evidence that mutations in mtDNA are involved in complex traits such as neurodegeneration, ageing and cancer. Mutations in the human mitochondrial genome are known to cause an array of diverse disorders, most of which are maternally inherited, and all of which are associated with defects in oxidative energy metabolism. It is now emerging that somatic mutations in mitochondrial DNA (mtDNA) are also linked to other complex traits, including neurodegenerative diseases, ageing and cancer. Here we discuss insights into the roles of mtDNA mutations in a wide variety of diseases, highlighting the interesting genetic characteristics of the mitochondrial genome and challenges in studying its contribution to pathogenesis.