Carbon Catabolite Repression in Yeast is Not Limited to Glucose

Kobi Simpson-Lavy,Martin Kupiec

doi:10.1038/s41598-019-43032-w

Abstract

Cells adapt their gene expression and their metabolism in response to a changing environment. Glucose represses expression of genes involved in the catabolism of other carbon sources in a process known as (carbon) catabolite repression. However, the relationships between “poor” carbon sources is less characterized. Here we show that in addition to the well-characterized glucose (and galactose) repression of ADH2 (alcohol dehydrogenase 2, required for efficient utilization of ethanol as a carbon source), ADH2 expression is also inhibited by acetate which is produced during ethanol catabolism. Thus, repressive regulation of gene expression occurs also between “poor” carbon sources. Acetate repression of ADH2 expression is via Haa1, independently from the well-characterized mechanism of AMPK (Snf1) activation of Adr1. The response to extracellular acetate is attenuated when all three acetate transporters (Ady2, Fps1 and Jen1) are deleted, but these deletions do not affect the acetate response resulting from growth with glucose or ethanol as the carbon source. Furthermore, genetic manipulation of the ethanol catabolic pathway affects this response. Together, our results show that acetate is sensed intracellularly and that a hierarchical control of carbon sources exists even for “poor” carbon sources.

Highlights

Cells have evolved to respond appropriately to changes to both their intracellular and extracellular environments via multiple sensing mechanisms
The inhibition of ADH2 expression by glucose via the inactivation of Snf[1] has been well-characterized (Snf[1] is needed to activate the Adr[1] and Cat[8] transcription factors)[44], it is still unclear whether ADH2 expression requires a positive signal from the poor carbon source
Whereas earlier work demonstrated that abolition of glucose repression results in constitutive ADH2 expression[46], and that ADH2 is induced by a variety of carbon sources including those whose metabolism does not involve Adh[247], we observed that even in the absence of any carbon source ADH2 is highly expressed (Fig. 1a), suggesting a lack of any positive signaling mechanism

Summary

Introduction

Cells have evolved to respond appropriately to changes to both their intracellular and extracellular environments via multiple sensing mechanisms. In the yeast Saccharomyces cerevisiae, when glucose is present in the extracellular medium, uptake and catabolism of other carbon sources is repressed[6] via three signaling pathways; inhibition of AMPKSnf[1 14], activation of PKA15,16, and the regulation of transporter expression and stability at the plasma membrane by the yeast casein kinases Yck[1] and Yck[217]. Alterations in gene expression of the ethanol-acetate pathway have been previously shown to affect acetic acid production during fermentation[20]. A search for genes that can reduce this toxicity found that overexpression of the Haa[1] transcription factor results in resistance to acetic acid and increased ethanol yield, by mediating increased expression of target genes[27].

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Conclusion