Superoxide production by mitochondria in the presence of nitric oxide forms peroxynitrite

The mitochondrial respiratory chain continually produces superoxide leading to high levels of mitochondrial oxidative stress. This oxidative damage has been attributed to the formation of hydroxyl radicals and hydrogen peroxide from superoxide. Alternatively, mitochondrial superoxide may react with nitric oxide forming the potent oxidant peroxynitrite, thus damaging mitochondrial protein, lipid and DNA. To test this hypothesis we induced mitochondrial superoxide formation in the presence of nitric oxide. Here we demonstrate that mitochondrial superoxide reacts with nitric oxide to form peroxynitrite, suggesting that mitochondria may be a significant intracellular source of peroxynitrite.