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Metabolic alterations have been recognized to underly the etiology of many diseases. Herein, cellular energy dissipation was evaluated as a novel non-specific global biomarker of metabolic alterations. Energy dissipation, measured as heat by microcalorimetry, was maximal during Saccharomyces cerevisiae adaptation to growth conditions before fast proliferation took place. This response was further augmented by 95 % in media where nutrient assimilation was more difficult, and by 133 % under sub-optimal non-carbon nutrient levels. In this last case, the increase in energy dissipation (1) reflected changes in amino acid and glycolytic metabolism and (2) anticipated changes in the growth curve significantly later observed by traditional microbiological measurements. It was, therefore, an early marker of adaptive responses that compensated for sub-optimal nutrient levels and maintained phenotypic stability. Compensatory responses buffer systems against perturbations and delay the onset of diseases. Microcalorimetry can, therefore, provide a biomarker development platform for early disease-diagnosis.

Cellular growth is usually separated in well-defined phases. For microorganism like Saccharomyces cerevisiae, two phases usually defined are (1) a lag phase, in which no growth is observed and cells adapt to a new environment, followed by (2) an exponential phase, in which rapid proliferation occurs. Here we investigate whether these well-defined phases are uniform. By using flow-microcalorimetry, we found that the metabolic profile of the culture is continuously changing, both in the lag and exponential phases of growth. Along the lag phase there is a continuous increase in the energy that is dissipated irreversibly as heat, while in the exponential phase the opposite occurs. We also confirm recent observations that the oxidative component of metabolism decreases along the exponential phase. Interestingly, nutrient limitation further decreases the amount of energy that is dissipated irreversibly. Altogether, this points to a picture in which cells respond rapidly to minute environmental changes by adjusting their metabolic profile.

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