12 October 2012
Nikolai Slavov
Oudenaarden group
MIT
Most cells can derive energy from glucose either by oxidizing it completely to carbon dioxide and water, i.e. oxidative phosphorylation, or by fermenting the glucose to ethanol/lactate. It has been known for a century that under some conditions cells ferment glucose into ethanol/lactate even in the presence of sufficient oxygen to support oxidative phosphorylation. This process, known as aerobic glycolysis, appears surprising since oxidative phosphorylation has higher energy yield per glucose molecule than fermentation. Thus, numerous studies have suggested many elegant mechanisms that, theoretically, can rationalize aerobic glycolysis and yet some of these mechanisms are mutually incompatible. Instead of examining existing hypotheses and models, we measured metabolic fluxes, rates of respiration and fermentation in budding yeast growing across a wide range of conditions, aiming to identify experimentally trade-offs associated with aerobic glycolysis. We used these data to eliminate theoretical possibilities and constrain as much as possible the systems-level physiological responses and adaptations of cell growth to different nutrient environments and growth rates. Our flux data, combined with simple analysis based on mass-conservation, suggest inherent trade-offs in respiration and fermentation. I will discuss how some of these trade-offs can be understood in terms of first principles.