Mitochondrial oxidative stress. In the mitochondria, superoxide can be produced by respiratory complexes. Complex I in the brain and complex III in the heart and lung seem to be the primary sources of mitochondrial superoxide production. Superoxide is detoxified by manganese superoxide dismutase (MnSOD) to hydrogen peroxide (H2O2) in the mitochondria. Glutathione peroxidases (GPxs) convert hydrogen peroxide to water. Nitric oxide (NO) generated from (mitochondrial) nitric oxide synthase (mt)NOS can compete with MnSOD and form peroxynitrite (ONOO-). Peroxynitrite in turn initiates thiol oxidation or nitrosylation and tyrosine nitration. C, cytochrome c; O2-, superoxide; Q, ubiquinone.