RESUMEN
Mitochondrial respiratory chain defects are an important cause of inherited disorders affecting approximately 1 in 5000 people in the UK population. Collectively these disorders are termed 'mitochondrial diseases' and they result from either mitochondrial DNA mutations or defects in nuclear DNA. Although they are frequently multisystem disorders, neurological deficits are particularly common, wide-ranging and disabling for patients. This review details the manifold neurological impairments associated with mitochondrial disease, and describes the efforts to understand how they arise and progressively worsen in patients with mitochondrial disease. We describe advances in our understanding of disease pathogenesis through detailed neuropathological studies and how this has spurred the development of cellular and animal models of disease. We underscore the importance of continued clinical, molecular genetic, neuropathological and animal model studies to fully characterize mitochondrial diseases and understand mechanisms of neurodegeneration. These studies are instrumental for the next phase of mitochondrial research that has a particular emphasis on finding novel ways to treat mitochondrial disease to improve patient care and quality of life.