[Oxidative damage of mitochondrial DNA: the result or consequence of enhanced generation of reactive oxygen species]

According to mitochondrial theory of ageing the ageing process results from accumulation of mitochondrial DNA (mtDNA) damage. Close vicinity of mtDNA molecule to the source of reactive oxygen species, electron transport chain, potentiates degradation of nucleic acid chemical components. The most common types of mtDNA damage generated are point mutations as a result of oxidative modifications of purines and pyrimidines (transitions as well as transversions), but also deletions and rarely insertions. Since mtDNA codes for subunits of respiratory chain enzymes, its lesions can alter homeostasis of the cell resulting in a decrease of intracellular ATP. Growing evidence indicates the role of mtDNA mutations in elevated production of reactive oxygen species, which in turn are proved to increase the number of mtDNA mutations. This mechanism gave the basis for theory of a vicious cycle: ROS<-->mutations of mtDNA