Methylglyoxal-Scavenging Enzyme Activities Trigger Erythroascorbate Peroxidase and Cytochrome c Peroxidase in Glutathione-Depleted Candida albicans

gamma-Glutamylcysteine synthetase (Gcs1) and glutathione reductase (Glr1) activity maintains minimal levels of cellular methylglyoxal in Candida albicans. In glutathione-depleted Delta gcs1, we previously saw that NAD(H)-linked methylglyoxal oxidoreductase (Mgd1) and alcohol dehydrogenase (Adh1) are the most active methylglyoxal scavengers. With methylglyoxal accumulation, disruptants lacking MGD1 or ADH1 exhibit a poor redox state. However, there is little convincing evidence for a reciprocal relationship between methylglyoxal scavenger genes-disrupted mutants and changes in glutathione-(in)dependent redox regulation. Herein, we attempt to demonstrate a functional role for methylglyoxal scavengers, modeled on a triple disruptant (Delta mgd1/Delta adh1/Delta gcs1), to link between antioxidative enzyme activities and their metabolites in glutathione-depleted conditions. Despite seeing elevated methylglyoxal in all of the disruptants, the result saw a decrease in pyruvate content in Delta mgd1/Delta adh1/Delta gcs1 which was not observed in double gene-disrupted strains such as Delta mgd1/Delta gcs1 and Delta adh1/Delta gcs1. Interestingly, Delta mgd1/Delta adh1/Delta gcs1 exhibited a significantly decrease in H2O2 and superoxide which was also unobserved in Delta mgd1/Delta gcs1 and Delta adh1/Delta gcs1. The activities of the antioxidative enzymes erythroascorbate peroxidase and cytochrome c peroxidase were noticeably higher in Delta mgd1/Delta adh1/Delta gcs1 than in the other disruptants. Meanwhile, Glr1 activity severely diminished in Delta mgd1/Delta adh1/Delta gcs1. Monitoring complementary gene transcripts between double gene-disrupted Delta mgd1/Delta gcs1 and Delta adh1/Delta gcs1 supported the concept of an unbalanced redox state independent of the Glr1 activity for Delta mgd1/Delta adh1/Delta gcs1. Our data demonstrate the reciprocal use of Eapx1 and Ccp1 in the absence of both methylglyoxal scavengers; that being pivotal for viability in non-filamentous budding yeast.