Thermochimica Acta 394 (2002) 113–121 Control of growth yield of yeast on respiratory substrate by mitochondrial content Laurent Dejean, Odile Bunoust, Jacques Schaeffer, Bernard Guérin, Michel Rigoulet, Bertrand Beauvoit ∗ Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS, Université Victor Segalen, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France Received 10 September 2001; received in revised form 14 January 2002; accepted 2 March 2002 Abstract 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. Overacti- vation 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. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Yeast; Microcalorimetry; Enthalpic growth yield; Mitochondria; Oxidative phosphorylation; cAMP 1. Introduction Microbial growth is a striking adaptation of mi- croorganisms to environmental changes to reach a ∗ Corresponding author. Tel.: +33-5569-990-33; fax: +33-55699-9040. E-mail address: bertrand.beauvoit@ibgc.u-bordeaux2.fr. (B. Beauvoit). compromise between growth rate, growth yield and thermodynamic growth efficiency. For decades, quan- titative and theoretical tools have been developed to describe such phenomena. For instance, Metabolic Control Analysis has been widely used to quantify the kinetic control of the growth rate that may arise dur- ing variations of the enzymatic equipment of growing cells (e.g. see [1–3] for the F 1 F 0 -type H + ATP syn- thase, P-type H + ATPase and bc1-respiratory chain 0040-6031/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0040-6031(02)00244-7