Journal Article

Human mitochondrial DNA: roles of inherited and somatic mutations

Schon, Eric A., DiMauro, Salvatore, Hirano, Michio

2012

Overview

Key Points Mitochondrial diseases are among the most common genetic disorders. They can result from mutations in the mitochondrial genome or nuclear genome. The mitochondrial genome needs to be understood in terms of population genetics, rather than Mendelian genetics; this makes it particularly challenging to understand mitochondrial diseases. Mutations in mitochondrial DNA (mtDNA) accumulate over the lifetime of an individual and are now implicated in ageing and neurodegeneration. There is current interest in exploring possible roles of mitochondrial genetic variation in susceptibility to complex diseases, but the evidence remains uncertain at present. The literature documenting the accumulation of mtDNA mutations in tumours needs to be interpreted with caution. 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/726/2129 / 631/208/737 / 68 / Aging - genetics / Aging - metabolism / Agriculture / Animal Genetics and Genomics / Antibody diversity / Bats / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Disease / DNA, Mitochondrial - genetics / DNA, Mitochondrial - metabolism / Electron Transport / Fundamental and applied biological sciences. Psychology / Gene Function / Gene mutations / Genes / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome, Mitochondrial / Genomes / Germ-Line Mutation / Health aspects / Heredodegenerative Disorders, Nervous System - genetics / Heredodegenerative Disorders, Nervous System - metabolism / Human Genetics / Humans / Mitochondria / Mitochondrial Diseases - genetics / Mitochondrial Diseases - metabolism / Mitochondrial DNA / Models, Biological / Models, Genetic / Morphology / Mutation / Neoplasms - genetics / Neoplasms - metabolism / Oxidative Phosphorylation / Pathology, Molecular / review-article / Roles