Oxidative Stress, Mitochondria, and Apoptosis

Article type: Research Article

Authors: Richter, Christoph

Affiliations: Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Universitätstr. 16, CH-8092 Zürich, Switserland

Abstract: This article emphasizes the importance of mitochondria, the cellular ATP level, 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 altered cellular Ca2+ homeostatis, considered to be mediators of apoptosis, synergistically decrease the mitochondrial membrane potential and lower the cellular ATP level. Conversely, stabilization of the mitochondrial membrane potential, e.g., by the protooncogene bcl-2, prevents cell death. An important process underlying mitochondrial destabilization is oxidant-induced mitochondrial Ca2+ release followed by re-uptake ("Ca2+ cycling"). Tumor necrosis factor-a induces oxygen radicals in mitochondria through ceramides, and the recently discovered mitochondrial nitric oxide synthase profoundly stimulates Ca2+ release from mitochondria through formation of nitrogen monoxide and peroxynitrite.

Keywords: Ca2+, ceramides, cytochrome c, membrane potential, reactive nitrogen, reactive oxyogen

Journal: Restorative Neurology and Neuroscience, vol. 12, no. 2-3, pp. 59-62, 1998