NAD+-linked alcohol dehydrogenase 1 regulates methylglyoxal concentration in Candida albicans

• Methylglyoxal dehydrogenase activity is observed only in the glutathione-depleted cells.
• The first report on methylglyoxal-oxidizing alcohol dehydrogenase in microorganisms.
• Candida alcohol dehydrogenase is involved in methylglyoxal oxidation and reduction.
• Accumulated methylglyoxal inhibits cell growth in alcohol dehydrogenase disruptants.
• Alcohol dehydrogenase regulates cell cycle by catalyzing methylglyoxal in C. albicans.

We purified a fraction that showed NAD+-linked methylglyoxal dehydrogenase activity, directly catalyzing methylglyoxal oxidation to pyruvate, which was significantly increased in glutathione-depleted Candida albicans. It also showed NADH-linked methylglyoxal-reducing activity. The fraction was identified as a NAD+-linked alcohol dehydrogenase (ADH1) through mass spectrometric analyses. In ADH1-disruptants of both the wild type and glutathione-depleted cells, the intracellular methylglyoxal concentration increased significantly; defects in growth, differentiation, and virulence were observed; and G2-phase arrest was induced.