LAUSR

Obviously the EMBO/EMBL Symposium “Metabolism Meets Epigenetics” left more of an impression on me than at first I thought; perhaps that was inevitable given the enormously wide range of biological phenomena that are starting to be explored at the interface of the two fields: from collective behaviour of ant colonies to immunology and cancer, with yeast in the middle, so to speak. It was the talks on the yeast metabolic cycle that got me thinking about the topic of the present editorial. Essentially, the yeast metabolic cycle has three phases: Ox (oxidative, respiratory), R/B (reductive, building) and R/C (reductive, charging), and it is independent from circadian oscillations. Its function is thought to be to create a dynamically poised state in which the cell can react more quickly to changing energy demands or supply of nutrients. Cancer cells also become remarkably sensitive to their metabolic needs and constraints, and they are increasingly viewed as entities in an micro-ecosystem (the cancer cell niche, and then the larger tissue environment; finally the journey and re-settlement that ismetastasis) – amicroenvironment that never stays the same, and that poses threats and opportunities to the cancer cell. I started to wonder whether cancer cells might also have a metabolic cycle. If one likens cancer cells to unicellular organisms “fighting it out” in an unforgiving environment, one might easily entertain the notion of them having similar metabolic controls to yeast. In the presence of sufficient glucose, the metabolism of S. cerevisiae is primarily fermentative (almost exclusively glycolysis), even in the presence of sufficient oxygen for oxphos. The reason, we can surmise, is that glycolysis is a “cheap” way to make energy and intermediates of anabolism (amino acids, DNA bases and lipids for cell growth and division, for example). Yeast is, in fact, a goodmodel for studying glucose sensing pathways. If nonfermentable carbon sources (e.g., lipids, fats, oils) are all that the yeast cells get, then they switch on the oxidative phosphorylation in their mitochondria – a step that is relatively costly to the cell compared withmere glycolysis, because protein synthesis for the electron transport chain is upregulated from nuclear and mitochondrial genes. Given sufficient fermentable substrates again, the yeast will happily switch back to majority glycolysis. That cancer cells switch (or, more accurately, tune the balance) between glycolysis and oxphos is no coincidence.