Why Mitochondrial DNA Is Needed

At age five a seemingly healthy boy inexplicably began to lose his hearing, which disappeared entirely before he turned 18. In the interim, he was diagnosed as hyperactive and suffered occasional seizures. By the time he was 23, his vision had declined; he had cataracts, glaucoma and progressive deterioration of the retina. Within five years he had experienced severe seizures, and his kidneys had failed. He died at 28 from his kidney disorder and a systemic infection. At the root of his problems was a minute imperfection in his genes—but not in the familiar ones residing in the long, linear strings of chromosomal DNA that populate every cell nucleus. Instead he was killed by an abnormality in tiny circles of lesser known DNA located in his mitochondria, the power plants of cells. Each such circle contains the genetic blueprints for 37 of the molecules mitochondria need to generate energy. Scientists have known since 1963 that mitochondria in animals harbor their own genes, but errors in those genes were not linked to human ailments until 1988. In that year, my laboratory at Emory University traced the origin of a form of young-adult blindness (Leber’s hereditary optic neuropathy) in several families to a small inherited mutation in a mitochondrial gene. At about the same time, Ian J. Holt, Anita E. Harding and John A. Morgan-Hughes of the Institute of Neurology in London connected deletion of relatively large segments of the mitochondrial DNA molecule to progressive muscle disorders.