Mitochondrial DNA mutations in the pathogenesis of human disease

The coding sequence for the human mitochondrial genome (mtDNA) was publishe d in 1981. Within a decade, the first pathogenic mtDNA mutations were descr ibed in humans with sporadic and maternally inherited disease. The last ten years has seen a profusion of reports describing new pathogenic mutations associated with a diverse range of clinical phenotypes. Although we have se en great advances in our understanding of the molecular mechanisms involved in the pathogenesis of mtDNA disease, we are only just beginning to tackle some of the more difficult questions. In this review we describe recent ad vances in our understanding of mtDNA disease and highlight ways that this k nowledge might lead to novel therapies in the future.