Increased intracellular calcium active NOS to generate NO. Superoxide (⁠⁠) interacts with NO to form ONOO⁻ and subsequently leads to generation of ^·OH⁻. ONOO⁻ itself can target the mitochondrial respiratory complexes directly. SOD also converts into H₂O₂, where excessive build-up of H₂O₂ leads to an exacerbated generation of ^·OH⁻ via the Fenton reaction. All of these reactive oxygen and nitrogen species contribute to lipid peroxidation, DNA damage and harmful protein oxidation in addition to influencing the release of pro-apoptotic proteins from the mitochondria to initiate cell death.