The neutralization of ROS occurs at both intramitochondrial sites by antioxidant enzymes, manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) and within the cytosol by CuSOD, GPx and catalase. Association of BAX with mitochondria is prevented by anti-apoptogenic Bcl family of proteins. This is followed by the release of cytochrome c and apoptosis-inducing factor (AIF) from the mitochondria to the cytosol with subsequent activation of the caspases initiating cell self-digestion and nuclear DNA fragmentation leading to apoptotic cell death. Elevated levels of mitochondrial calcium levels as well as excessive ROS (generated at respiratory complex I and III sites) as shown also promote the PTP opening. Cellular signals including ROS, and UV-induced DNA damage and a variety of «death signals» trigger the apoptotic pathway by modulation of the binding of proapoptogenic proteins (e.g.
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