Mitochondria as source of free radicals

Mitochondria have been considered to be mediators of cell metabolism involved in important life processes, such as aging, cell death, and persistent chronic diseases, in addition to their main function of producing ATP. Chronic diseases cause mutations or deletions in the mitochondrial genome (mt genome), which is believed to accumulate damage from long-term oxidative stress. Because mitochondrial DNA (mtDNA) encodes 13 genes for proteins that comprise a part of the electron transport chain (ETC), damage to these genes causes ETC impairment. Treatment with ETC inhibitors (rotenone, 3- nitropropionic acid, thenoyltrifluoroacetone, antimycin A, and sodium cyanide) generates increased intracellular reactive oxygen species (ROS). A significant increase in ROS was also observed in cells lacking mtDNA and mtDNA-deleted cells compared with their parental cells, although no increase was observed in cybrids. Furthermore, cells transfected with cDNA encoding manganese superoxide dismutase had decreased levels of ROS. These results suggest that more ROS are generated from mitochondria in cells that have the ETC impaired either by inhibition or damage to the mtDNA.