The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression

Abstract

During the last decades a considerable amount of research has been focused on cancer. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display enhanced glycolytic activity and impaired oxidative phosphorylation (Warburg effect). Therefore, it seems reasonable that disruption of glycolysis might be a promising candidate for specific anti-cancer therapy. Nevertheless, the concept of aerobic glycolysis as the paradigm of tumor cell metabolism has been challenged, as some tumor cells exhibit high rates of oxidative phosphorylation. Mitochondrial physiology in cancer cells is linked to the Warburg effect. Besides, its central role in apoptosis makes this organelle a promising "dual hit target" to selectively eliminate tumor cells. From a metabolic point of view, the fermenting yeast Saccharomyces cerevisiae and tumor cells share several features. In this paper we will review these common metabolic properties as well as the possible origins of the Crabtree and Warburg effects.

Simultaneous Steady-state and Dynamic 13C NMR Can Differentiate Alternative Routes of Pyruvate Metabolism in Living Cancer Cells

“…Under the conditions used here, both anaerobic and aerobic pyruvate metabolism were acutely and reversibly impacted by the high glycolytic flux of SFxL cells. The lack of a fixed constraint on mitochondrial pyruvate metabolism recalls the Crabtree effect, in which a large glucose supply reversibly suppresses oxidative metabolism in yeast and cancer cells (22). Importantly, changes in pyruvate metabolism could be partially reversed in the presence of glucose by inhibiting Akt, the kinase that stimulates glycolysis in SFxL cells.…”

Mitochondrial O-GlcNAc Transferase (mOGT) Regulates Mitochondrial Structure, Function, and Survival in HeLa Cells

“…5B). Maximal glycolysis can be experimentally induced by the addition of the ATP synthase inhibitor oligomycin through a phenom- enon that is akin to the Crabtree effect (34). Interestingly, although pan-OGT siRNA-transfected cells showed a robust increase in maximal glycolytic capacity and glycolytic reserve compared with NT siRNA-transfected cells, cells transfected with mOGT siRNAs showed only a modest, non-significant increase ( 2J).…”

Are cultured human myotubes far from home?

“…It is well known that cancer cells in particular, but also other cells, become highly glycolytic when grown in high glucose concentrations. Glucose inhibits oxidative phosphorylation, a phenomenon known as the Crabtree effect (Diaz-Ruiz, et al, 2011, Ibsen, 1961. This effect can possibly be avoided by growing cells in media with other nutrients, such as amino acids, lipids or lactate.…”