The Warburg effect: a signature of mitochondrial overload.

Proliferating cells have increased mitochondrial activity relative to quiescent cells. Metabolic pathways in mitochondria are saturated in proliferating cells exhibiting the Warburg effect. Mitochondrial activity is constrained by the flux of NAD+ turnover in proliferating cells. The Warburg effect occurs in proliferating cells because glycolysis outpaces the maximum rate of glucose oxidation. A long-standing question in cancer biology has been why oxygenated tumors ferment the majority of glucose they consume to lactate rather than oxidizing it in their mitochondria, a phenomenon known as the 'Warburg effect.' An abundance of evidence shows not only that most cancer cells have fully functional mitochondria but also that mitochondrial activity is important to proliferation. It is therefore difficult to rationalize the metabolic benefit of cancer cells switching from respiration to fermentation. An emerging perspective is that rather than mitochondrial metabolism being suppressed in tumors, as is often suggested, mitochondrial activity increases to the level of saturation. As such, the Warburg effect becomes a signature of excess glucose being released as lactate due to mitochondrial overload. [ABSTRACT FROM AUTHOR]