Mitochondrial ROS are important mediators of chromosomal DNA damage

Mitochondria not only produce ATP but also generate major reactive oxygen species (ROS) and participate in redox balance. The remaining ROS, including NADPH oxidase, xanthine oxidase, and cytochrome p450, are generated in the cytosol via the Fenton reaction and peroxisomes. Excessive ROS production or deficiency of antioxidant enzymes decreases the redox balance and causes a cellular oxidative stress state. Sustained oxidative stress causes damage to DNA, proteins, and membrane lipids. Previous studies have shown that mitochondrial ROS plays an important role in nuclear DNA damage. However, recent research has reported that mitochondrial H 2 O 2 release does not directly cause damage to chromosomal DNA. Here, we studied the effects of mitochondrial ROS induced by menadione (MEN), a mitochondrial superoxide inducer, on DNA oxidation damage. We found that ROS released in the cytosol from mitochondria can directly or indirectly damage chromosomal DNA when the antioxidant system collapses under non physiological conditions.