BCL-2: pro-or anti-oxidant?

Bcl-2 is recognized as an oncoprotein via its ability to impede death signaling by sequestrating proapoptotic 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.