Yeast cells display a regulatory mechanism in response to methylglyoxal

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Abstract
Methylglyoxal (MG), a glycolytic by-product, is an extremely toxic compound. This fact suggests that its synthesis and degradation should be tightly controlled. However, little is known about the mechanisms that protect yeast cells against MG toxicity. Here, we show that in Saccharomyces cerevisiae, MG exposure increased the internal MG content and activated the expression of GLO1 and GRE3, two genes involved in MG detoxification; GPD1, the gene for glycerol synthesis; and TPS1 and TPS2, the trehalose pathway genes. This response was specific as demonstrated by the analysis of marker genes and effectors of the general stress response. Physiological experiments with MG-treated cells showed that this compound triggers the overproduction of glycerol. Furthermore, a gpd1 gpd2 double mutant showed enhanced MG contents compared with the wild-type. Overall, these results appeared to indicate that up-variations in the intracellular content of the toxic compound are perceived by the cell as a primary signal to trigger the transcriptional response. In agreement with this, MG-instigated GPD1 activation was enhanced in strains lacking GLO1, and this effect correlated with the internal MG content. Finally, induction of GPD1, TPS1 and GRE3, and enhanced MG contents were also observed in low-glucose-growing cells subjected to a sudden increase in glucose availability. The implications of this regulatory mechanism on protection against MG are discussed.