ABSTRACT
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A.
INTRODUCTION
Mitochondria are essential cellular organelles that convert carbohydrates, lipids, and proteins into usable energy in the form of adenosine triphosphate (ATP) through aerobic metabolism. They originated from aerobic bacteria that formed symbiotic relationships with eukaryotic cells, which benefited from their newly acquired capacity to utilize oxygen. This relationship is unique due, in part, to the fact that mitochondria are the only mammalian subcellular organelles-aside from the nucleus-that contain genetic material. Although mitochondria contain their own DNA (mtDNA), over evolutionary time most of the genes necessary for mitochondrial functions have been transferred to the nuclear DNA (nDNA). Therefore, mitochondrial diseases, that is, genetic diseases resulting in mitochondrial dysfunction, can be due to mutations in either genome. The ubiquitous nature of mtDNA and the peculiar rules of mitochondrial genetics contribute to the extraordinary clinical heterogeneity of mitochondrial disorders. Impairment of oxidative ATP production affects mainly tissues with high-energy requirements, such as skeletal muscle and brain, and results in mitochondrial myopathies or mitochondrial encephalomyopathies. Nevertheless, these disorders affect virtually every organ system in varying combinations resulting in protean clinical manifestations.
