Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells.
Mitochondrial respiration, the key process behind cellular energy production, is critical for cell proliferation, growth and survival. However, the regulation of mitochondrial respiratory function in tumor cells is not well understood. In this study, we propose a model whereby tumor cells possess the capacity to fine-tune the balance between energy demands and mitochondrial reactive oxygen species (ROS) status, to maintain a milieu optimal for survival. This is achieved through the moderation of mitochondrial respiration, depending on the ROS context within the organelle, with the main players being Bcl-2 and cytochrome c oxidase (COX). We report a higher level of COX activity, oxygen consumption and mitochondrial respiration in tumor cells overexpressing Bcl-2. Transient overexpression, gene silencing and pharmacological inhibition of Bcl-2 corroborate these findings. Interestingly, Bcl-2 is also able to regulate mitochondrial respiration and COX activity in the face of mounting ROS levels, triggered by mitochondrial complex inhibitors. In this respect, it is plausible to suggest that Bcl-2 may be able to create an environment, most suited for survival by adjusting mitochondrial respiration accordingly to meet energy requirements, without incurring an overwhelming, detrimental increase in intracellular ROS.
Chen
Z X
ZX
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Pervaiz
S
S
D045744:Cell Line, Tumor; D019069:Cell Respiration; D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013481:Superoxides; D045304:Cytochromes c; D003576:Electron Transport Complex IV