Redox aspects of Bcl-2 function

Antioxid Redox Signal. Fall 2000;2(3):537-50. doi: 10.1089/15230860050192314.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis
  • Glutathione / metabolism
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Models, Biological
  • Oxidation-Reduction*
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Signal Transduction

Substances

  • Antioxidants
  • Proto-Oncogene Proteins c-bcl-2
  • Glutathione