Redox aspects of Bcl-2 function.
The oncogene Bcl-2 has attracted recent research attention as recognition of the importance of Bcl-2 control over apoptosis commitment in disease development and clinical response to therapy has been targeted for pharmacological intervention. Much of the basic science research regarding Bcl-2 has focused on the role that Bcl-2 plays in directly regulating mitochondrial function. This has come about because of Bcl-2's localization to mitochondrial membranes and its reported interaction with the mitochondrial megachannel. During the time that the mitochondrial function of Bcl-2 was being investigated, a smaller, yet potentially as important, role for Bcl-2 was being pursued by investigators who were following up the initial study of Bcl-2 knockout mice. These mice expressed a phenotype consistent with that of mice exposed to chronic oxidative stress. This research into the redox aspects of Bcl-2 function has led to a hypothesis that Bcl-2-expressing cells have enhanced antioxidant capacities that suppress oxidative stress signals generated during the initiation phase of many apoptotic pathways. This review will further develop the idea of Bcl-2's role in regulating cellular redox pathways associated with apoptosis, as well as integrate recently reported evidence that ties the antioxidant effects of Bcl-2 to mitochondrial function, thereby unifying both mitochondrial and redox aspects of Bcl-2 function.
Voehringer
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Department of Genetics, Stanford University School of Medicine, CA 94305-5318, USA. Voehringer@stanford.edu
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction
D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D005978:Glutathione