The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast

Molecular Biology of the Cell
Adhiraj RoyJeong-Ho Kim

Abstract

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. 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. These results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. In addition, the inhibitory effect of MG on the glucose sensors is greatly enhanced in cells lacking Glo1, a key component of the MG detoxification system. 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 d...Continue Reading

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Citations

Mar 23, 2017·Molecular Microbiology·Sara Manzanares-EstrederMarkus Proft
Jun 21, 2017·Current Genetics·Amparo Pascual-AhuirMarkus Proft
Apr 2, 2020·TheScientificWorldJournal·Halyna Semchyshyn
Feb 28, 2021·Cell Communication and Signaling : CCS·Sanjar Batirovich MadrakhimovTae Kwann Park
Nov 7, 2020·World Journal of Microbiology & Biotechnology·Siqing LiuNasib Qureshi

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Methods Mentioned

BETA
PCR
confocal microscopy
fluorescence microscopy
ubiquitination

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ImageJ
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