Control of growth yield of yeast on respiratory substrate by mitochondrial content

It is well documented that the growth yield of microorganisms depends on the fraction of ATP utilized for cell maintenance compared to that used for biomass synthesis per se. During aerobic growth, the growth yield may also be a function of the yield of ATP synthesis by oxidative phosphorylation (i.e. ATP/O ratio), a parameter which can vary in vitro according to the functional steady state of mitochondria. In this respect, the enthalpic growth yield of yeast aerobic cultures has been assessed by direct microcalorimetry during the transition from exponential growth to stationary phase. Under these conditions, the ATP turnover largely decreased whereas, the growth yield remained quite constant. This steady yield was due to a decrease in the mitochondrial content throughout the transition period. The Ras/cAMP/PKA signaling pathway is known to regulate adaptations of yeast cells upon environmental and metabolic transitions. We further analyzed yeast mutants overactivated for this pathway under fully aerobic growth conditions. Overactivation induced a proliferation of mitochondria within the cells which was correlated with a high respiratory activity and a drop in the enthalpic growth yield. Taken together, these results indicate that mitochondria by themselves can behave as energy dissipative systems under conditions where the oxidative phosphorylation capacity largely exceeds the ATP needs for cell growth. These data emphasize the physiological importance of the regulation of mitochondrial biogenesis in the optimization of the growth yield versus growth rate.