Extracellular methylglyoxal toxicity in Saccharomyces cerevisiae: role of glucose and phosphate ions

Abstract

The purpose of this study was to investigate the behaviour of Saccharomyces cerevisiae in response to extracellular methylglyoxal. Cell survival to methylglyoxal and the importance of phosphates was investigated. The role of methylglyoxal detoxification systems and methylglyoxal-derived protein glycation were studied and the relation to cell survival or death was evaluated. Extracellular methylglyoxal decreased cell viability, and the presence of phosphate enhanced this effect. D-glucose seems to exert a protective effect towards this toxicity. Methylglyoxal-induced cell death was not apoptotic and was not related to intracellular glycation processes. The glyoxalases and aldose reductase were important in methylglyoxal detoxification. Mutants lacking glyoxalase I and II showed increased sensitivity to methylglyoxal, while strains overexpressing these genes had increased resistance. Extracellular methylglyoxal induced non-apoptotic cell death, being unrelated to glycation. Inactivation of methylglyoxal-detoxifying enzymes by phosphate is one probable cause. Phosphate and D-glucose may also act through their complex involvement in stress response mechanisms. These findings contribute to elucidate the mechanisms of cell toxicity by methylglyoxal. This information could be useful to on-going studies using yeast as a eukaryotic cell model to investigate methylglyoxal-derived glycation and its role in neurodegenerative diseases.