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J Biol Chem. 1998 Jan 30;273(5):2977-83.

Expression of the glyoxalase I gene of Saccharomyces cerevisiae is regulated by high osmolarity glycerol mitogen-activated protein kinase pathway in osmotic stress response.

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  • 1Research Institute for Food Science, Kyoto University, Uji, Kyoto 611-0011, Japan.


Methylglyoxal is a cytotoxic metabolite derived from dihydroxyacetone phosphate, an intermediate of glycolysis. Detoxification of methylglyoxal is performed by glyoxalase I. Expression of the structural gene of glyoxalase I (GLO1) of Saccharomyces cerevisiae under several stress conditions was investigated using the GLO1-lacZ fusion gene, and expression of the GLO1 gene was found to be specifically induced by osmotic stress. The Hog1p is one of the mitogen-activated protein kinases (MAPKs) in S. cerevisiae, and both Msn2p and Msn4p are the transcriptional regulators that are thought to be under the control of Hog1p-MAPK. Expression of the GLO1 gene under osmotic stress was completely repressed in hog1Delta disruptant and was repressed approximately 80 and 50% in msn2Delta and msn4Delta disruptants, respectively. A double mutant of the MSN2 and MSN4 gene was unable to induce expression of the GLO1 gene under highly osmotic conditions. Glucose consumption increased approximately 30% during the adaptive period in osmotic stress in the wild type strain. On the contrary, it was reduced by 15% in the hog1Delta mutant. When the yeast cell is exposed to highly osmotic conditions, glycerol is synthesized as a compatible solute. Glycerol is synthesized from glucose, and a rate-limiting enzyme in glycerol biosynthesis is glycerol-3-phosphate dehydrogenase (GPD1 gene product), which catalyzes reduction of dihydroxyacetone phosphate to glycerol 3-phosphate. Expression of the GPD1 gene is also under the control of Hog1p-MAPK. Methylglyoxal is also synthesized from dihydroxyacetone phosphate; therefore, induction of the GLO1 gene expression by osmotic stress was thought to scavenge methylglyoxal, which increased during glycerol production for adaptation to osmotic stress.

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