Oxidative stress, mitochondria, and apoptosis

This article emphasizes the importance of mitochondria, the cellular ATP le vel, and the liberation of certain mitochondrial proteins for the execution phase of apoptosis. Destabilization of mitochondria results in release of these proteins. Oxidative stress and an altered cellular Ca2+ homeostasis, considered to be mediators of apoptosis, synergistically decrease the mitoc hondrial membrane potential and lower the cellular ATP Level. Conversely, s tabilization of the mitochondrial membrane potential, e.g., by the protoonc ogene bcl-2, prevents cell death. An important process underlying mitochond rial destabilization is oxidant-induced mitochondriar Ca2+ release followed by re-uptake ("Ca2+ cycling"). Tumor necrosis factor-alpha induces oxygen radicals in mitochondria through ceramides, and the recently discovered mit ochondrial nitric oxide synthase profoundly stimulates Ca2+ release from mi tochondria through formation of ni nitrogen monoxide and peroxynitrite.