Human Mitochondrial Mutations and Repair

One of the unique features of mitochondria is that they have their own genome. Mitochondrial DNA, just like its counterpart in the nucleus, is constantly exposed to damaging agents such as ionizing radiation, environmental toxins, as well as many therapeutic drugs. Mitochondrial DNA is also the main target of endogenous ROS. Oxidative damage and mutations are common in mtDNA. A wide spectrum of pathogenic mutations of mtDNA has been demonstrated and associated with common diseases such as diabetes, neurodegeneration, cancer, and aging. Although some of these mutations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells. Mutations can be the results of unrepaired damage to mtDNA. Evidence now clearly shows that mitochondria contain the machinery to repair the damage to their genomes caused by certain endogenous or exogenous damaging agents. In this review we provide general information about the human mitochondrial genome and susceptibility of mtDNA to damage, show the association of human mtDNA mutations with aging and diseases, describe the pathways and the proteins involved in mammalian mtDNA repair in normal and pathologic states, and discuss how modulation of mtDNA repair could be a powerful tool to better understanding of the biologic significance of mtDNA repair mechanisms for cellular defenses.