BCL-2: pro-or anti-oxidant?
Bcl-2 is recognized as an oncoprotein via its ability to impede death signaling by sequestrating pro-apoptotic proteins such as Bax and Bak as well as preserving mitochondrial outer membrane integrity. Recently, a growing body of evidence has evaluated the role of Bcl-2 in intracellular redox regulation and its downstream effects on life and death decisions in cancer cells. On the backdrop of these findings, we discuss here the classical anti-apoptotic role of Bcl-2 in malignant cells, and review the significance of Bcl-2-mediated regulation of tumor redox status. We discuss recent evidence that underscores a paradigm shift in the way cellular redox status impacts cell fate decisions via the effect of Bcl-2 on mitochondrial physiology. The ability of Bcl-2 to promote, modulate and optimize mitochondrial respiration under different redox states highlights the importance of mitochondrial bioenergetics, ROS and the roles they might play in the onset and/or maintenance of oncogenesis.
Chen
Zhi Xiong
ZX
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. phssp@nus.edu.sg
Pervaiz
Shazib
S
D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species