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.