Elevated energy costs of biomass production in mitochondrial respiration-deficientSaccharomyces cerevisiae

Abstract

Microbial growth requires energy for maintaining the existing cells and producing components for the new ones. Microbes therefore invest a considerable amount of their resources into proteins needed for energy harvesting. Growth in different environments is associated with different energy demands for growth of yeast Saccharomyces cerevisiae, although the cross-condition differences remain poorly characterized. Furthermore, a direct comparison of the energy costs for the biosynthesis of the new biomass across conditions is not feasible experimentally; computational models, on the contrary, allow comparing the optimal metabolic strategies and quantify the respective costs of energy and nutrients. Thus in this study, we used a resource allocation model of S. cerevisiae to compare the optimal metabolic strategies between different conditions. We found that S. cerevisiae with respiratory-impaired mitochondria required additional energetic investments for growth, while growth on amino acid-rich media was not affected. Amino acid supplementation in anaerobic conditions also was predicted to rescue the growth reduction in mitochondrial respiratory shuttle-deficient mutants of S. cerevisiae. Collectively, these results point to elevated costs of resolving the redox imbalance caused by de novo biosynthesis of amino acids in mitochondria. To sum up, our study provides an example of how resource allocation modeling can be used to address and suggest explanations to open questions in microbial physiology.

A continuous dynamic genome-scale model explains batch fermentations led by species of theSaccharomycesgenus

“…proteins, nucleic acids and carbohydrates, as: where GAM b is a modifiable parameter quantifying ATP costs in growth for non-polymerisation cellular processes. In our case, we adopted the value of 30 mmol · gDW −1 in agreement with the previous literature [Grigaitis et al, 2023]. The model provides essential information for identifying the different fermentation phases.…”

A fast method to distinguish between fermentative and respiratory metabolisms in single yeast cells

“…Yeast cells growing on excess glucose rely on glycolysis for 75% of their ATP generation, and therefore a temporary drop in ATP upon inhibition of respiration could have been expected but was not observed even though we estimate that 25% of ATP supply runs via respiration. 32 This may be explained by a rapid and sensitive activation of glycolysis, likely via AMP-mediated activation of phosphofructokinase. We expect that the inhibition by AA and the response of glycolysis through such metabolic regulation can act at the same time scales and render ATP homeostatically regulated.…”