Mitochondrial DNA mutations in human disease

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Abstract
Mutations in the maternally inherited mitochondrial genome (mtDNA), which contributes essential protein subunits to the enzyme complexes of oxidative phosphorylation, are an important cause of genetic disease. The clinical manifestations of mtDNA disorders are extremely variable; onset of symptoms might occur in infancy or in adulthood and can involve either a single organ or multiple tissues. Multiple copies (several hundreds or thousands) of the mitochondrial genome are present in individual cells. Many pathogenic mutations only affect a subset of mtDNA molecules, and there are differences in the mutation load between tissues that contribute to the observed clinical heterogeneity. Treatment options for mtDNA disorders are extremely limited, although several new approaches are being considered, including methods to prevent the transmission of pathogenic mutations from mother to offspring. Somatic mtDNA mutations in both human tumours and tissues from ageing individuals are increasingly being described. Recent data from a mouse model engineered to lose mtDNA sequence integrity supports a causal link between mtDNA mutations and the ageing process.