School of Medicine and Health Sciences Poster Presentations
Methylglyoxal Inhibits Expression of the Glucose Transporter Genes by Inactivating Rgt2/Snf3 Glucose Sensors
Poster Number
122
Document Type
Poster
Publication Date
3-2016
Abstract
Methylglyoxal (MG) is a highly reactive, cytotoxic dicarbonyl compound, mainly formed as a by-product of glycolysis. It is one of the most potent glycating agents and readily reacts with proteins, lipids and nucleic acids to form advanced glycation end products (AGEs). However, the molecular targets of MG are largely unknown. Glucose is the preferred carbon source of yeast Saccharomyces cerevisiae and can sense and utilize it efficiently over a broad range of concentrations. It prefers to ferment rather than oxidize glucose, even when oxygen is abundant. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of genes encoding glucose transporters (HXTs). Using molecular and cell biology approaches, including Western blotting, qRT-PCR analysis and fluorescence microscopy, we provide evidence that MG inhibits expression of the HXTs by inactivating the yeast glucose sensors Rgt2 and Snf3. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. Our results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. Under physiological conditions, MG is detoxified by the glyoxalase system into D-lactate, with glyoxalase 1 (Glo1) as the key enzyme in the anti-glycation defense. This study further indicates that the inhibitory effect of MG on the glucose sensors is greatly enhanced in the cells lacking Glo1. Thus, the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.
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Open Access
1
Methylglyoxal Inhibits Expression of the Glucose Transporter Genes by Inactivating Rgt2/Snf3 Glucose Sensors
Methylglyoxal (MG) is a highly reactive, cytotoxic dicarbonyl compound, mainly formed as a by-product of glycolysis. It is one of the most potent glycating agents and readily reacts with proteins, lipids and nucleic acids to form advanced glycation end products (AGEs). However, the molecular targets of MG are largely unknown. Glucose is the preferred carbon source of yeast Saccharomyces cerevisiae and can sense and utilize it efficiently over a broad range of concentrations. It prefers to ferment rather than oxidize glucose, even when oxygen is abundant. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of genes encoding glucose transporters (HXTs). Using molecular and cell biology approaches, including Western blotting, qRT-PCR analysis and fluorescence microscopy, we provide evidence that MG inhibits expression of the HXTs by inactivating the yeast glucose sensors Rgt2 and Snf3. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. Our results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. Under physiological conditions, MG is detoxified by the glyoxalase system into D-lactate, with glyoxalase 1 (Glo1) as the key enzyme in the anti-glycation defense. This study further indicates that the inhibitory effect of MG on the glucose sensors is greatly enhanced in the cells lacking Glo1. Thus, the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.
Comments
Presented at: GW Research Days 2016