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Background  Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated.    Methodology/Principal Findings  For this purpose, colonies of  Saccharomyces cerevisiae , which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death.    Conclusion/Significance  Thus, the Warburg effect might directly contribute to the initiation of cancer formation - not only by enhanced glycolysis - but also via decreased respiration in the presence of oxygen, which suppresses apoptosis.

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer