Relationship between increased aerobic glycolysis and DNA synthesis initiation studied using glycolytic mutant...

Reports from several laboratories have suggested increased rates of glycolysis play an essential part in the initiation of DNA synthesis. This is based on observations that aerobic glycolysis: (1) occurs at low rate in resting mammalian cells and at very high rate in tumour cells; (2) increases rapidly after DNA synthesis is initiated by addition of serum or purified growth factors, and (3) correlates with the expression of the transformed phenotype. Also, specific inhibitors of aerobic glycolysis prevent the initiation of DNA synthesis. To determine whether the rapid activation of phosphofructokinase--and therefore glycolysis--by purified growth factors is necessary for the initiation of cell proliferation, we have isolated and studied two classes of glycolytic mutants. The first, isolated from Chinese hamster fibroblasts, has a total block in the glycolytic pathway. The second, from hamster and Fisher rat fibroblasts maintains a permanent high rate of glycolysis. We have found that both classes of mutants retain normal control of DNA synthesis in response to serum. This dissociation indicates that growth-factor-stimulated glycolysis is not involved in the control of initiation of DNA synthesis and cell proliferation.