Dynamics of metabolism and its interactions with gene expression during sporulation in Saccharomyces cerevisiae

Abstract

The dynamics of metabolism has been shown to be involved in the triggering of events that are concurrent with sporulation of the budding yeast Saccharomyces cerevisiae. Indeed, quantitative correlations have been demonstrated between sporulation and the rate of carbon substrate or oxygen consumption, and the fluxes through gluconeogenic and glyoxylate cycle pathways. The results suggest that an imbalance between catabolic and anabolic fluxes influences the occurrence of the differentiation process. The hypothesis that the initiation of sporulation is triggered by the accumulation of an intracellular metabolite is confronted with the notion that intermediary metabolism and the expression of genes involved in sporulation interact to trigger the differentiation process. Several pieces of evidence indicate that derepression of the gluconeogenic pathway is crucial for the initiation of sporulation. One of the possible pathways through which glucose repression hampers sporulation might be the repression of gluconeogenesis as well as that of respiratory activity, in turn modulating the expression of IMEL++. The stages defined in the dynamics of sporulating cultures, namely readiness and commitment, are related to metabolic events associated with sporulation. An interpretation in terms of metabolic flux dynamics is given to the reversal of commitment occurring when the normal progression to sporulation is somehow blocked. The quantitative data are here integrated in a model attempting to simulate the dynamics of metabolic as well as cellular events during sporulation. The model is envisaged as a test of the hypothesis that an imbalance between anabolism and catabolism is involved in initiation of the sporulation process. It is proposed that such an imbalance may be a signal for differential gene expression associated with the differentiation pathway.