Mitochondrial oxidative stress and mitochondrial DNA

Mitochondria produce reactive oxygen species (ROS) under physiological conditions in association with activity of the respiratory chain in aerobic ATP production. The production of ROS is essentially a function of O₂ consumption. Hence, increased mitochondrial activity per se can be an oxidative stress to cells. Furthermore, production of ROS is markedly enhanced in many pathological conditions in which the respiratory chain is impaired. Because mitochondrial DNA, which is essential for execution of normal oxidative phosphorylation, is located in proximity to the ROS-generating respiratory chain, it is more oxidatively damaged than is nuclear DNA. Cumulative damage of mitochondrial DNA is implicated in the aging process and in the progression of such common diseases as diabetes, cancer, and heart failure.