Mitochondrial DNA mutations in disease and aging

Abstract The human mitochondrial genome involves over 1,000 genes, dispersed across the maternally inherited mitochondrial DNA (mtDNA) and the biparentally inherited nuclear DNA (nDNA). The mtDNA encodes 13 core proteins that determine the efficiency of the mitochondrial energy‐generating system, oxidative phosphorylation (OXPHOS), plus the RNA genes for their translation within the mitochondrion. The mtDNA has a very high mutation rate, which results in three classes of clinically relevant mtDNA mutations: recently deleterious germline line mutations resulting in mitochondrial disease; ancient regional variants, a subset of which permitted humans to adapt to differences in their energetic environments; and…