Interactions between carbon and nitrogen sources depend on RIM15 and determine fermentative or respiratory growth in Saccharomyces cerevisiae

Nutritional homeostasis is fundamental for alcoholic fermentation in Saccharomyces cerevisiae . Carbon and nitrogen have been related to this metabolic process; nevertheless, little is known about their interactions with the media and the energetic metabolism. Rim15p kinase is a point of convergence among different nutrient-activated signaling pathways; this makes it a target to investigate the relationship between nutritional status and energetic metabolism. To improve the current knowledge of nutrient interactions and their association with RIM15 , we validated the doubling time as an indicator of growth phenotype, confirming that this kinetic parameter can be related to the cellular bioenergetic status. This endorses the usefulness of a threshold in doubling time values as an indicator of fermentative (≤ 6.5 h) and respiratory growth (≥ 13.2 h). Using the doubling time as response variable, we find that (i) two second-order interactions between type and concentration of carbon and nitrogen sources significantly affected the growth phenotype of S. cerevisiae ; (ii) these metabolic interactions changed when RIM15 was deleted, suggesting a dependence on this gene; (iii) high concentration of ammonium (5% w / v ) is toxic for S. cerevisiae cells; (iv) proline prompted fermentative growth phenotype regardless presence or absence of RIM15 ; (v) RIM15 deletion reverted ammonium toxicity when cells were grown in glucose (10% w / v ); and (vi) RIM15 deletion improves fermentative metabolism probably by a partial inhibition of the respiration capacity. This study reveals the existence of synergic and diverse roles of carbon and nitrogen sources that are affected by RIM15 , influencing the fermentative and respiratory growth of S. cerevisiae .