A bioenergetic understanding of "aerobic glycolysis"

"Aerobic glycolysis" is a widely used term whose current meaning has drifted from its original usage in a way that has created confusion and inaccuracy. This drift has weakened "aerobic glycolysis" as a hypothesis-testing framework, despite the critical importance of glycolysis in understanding cellular bioenergetic behavior. Here, we examine the historical and contemporary uses of "aerobic glycolysis" and the related "Warburg effect". We argue that "aerobic glycolysis" as originally investigated was essentially a bioenergetic phenomenon. We review the bioenergetic model of glycolysis and mitochondrial respiration as ATP supply pathways operating together to meet cellular ATP demand. A bioenergetic view of aerobic glycolysis clarifies that it is not a less desirable contingency or indicator of pathology, but rather a part of a kinetically regulated system of cellular energy supply. On this basis, the operation of glycolysis under many different physiological and pathological conditions can be better interrogated and understood.