Carbon Catabolite Repression in Yeast is Not Limited to Glucose

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.