BCL-2 and glutathione: Alterations in cellular redox state that regulate apoptosis sensitivity

The importance of intracellular glutathione (GSH) in the pathology of disea se, particularly cancer, has long been appreciated. However the ubiquitous nature of GSH has made it difficult to ascribe to a specific molecular mech anism in disease fulfillment. In addition, in all but a few cases, the unde rlying genetic regulation of the cellular redox state disrupted in disease has not been well described. Early identification of the importance of intr acellular GSH to detoxification reactions has now led to investigating the potential importance that glutathione chemistry has on signal transduction and molecular regulation of cellular physiology. Here new relationships bet ween the cellular redox state and the apoptotic regulatory protein BCL-2 wi ll be described with emphasis on potential mechanisms by which GSH can alte r cellular physiology in addition to its role in detoxification. (C) 1999 E lsevier Science Inc.