Title |
Alcohol dehydrogenase 1 and NAD(H)-linked methylglyoxal oxidoreductase reciprocally regulate glutathione-dependent enzyme activities in Candida albicans |
Author |
Sa-Ouk Kang1* and Min-Kyu Kwak2* |
Address |
1Laboratory of Biophysics, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea, 2Department of Food and Nutrition, Institute of Food and Nutrition Science, Eulji University, Seongnam 13135, Republic of Korea |
Bibliography |
Journal of Microbiology, 59(1),76–91, 2021,
|
DOI |
10.1007/s12275-021-0552-7
|
Key Words |
alcohol dehydrogenase 1, Candida albicans, glutathione,
hyphal growth, methylglyoxal, NAD(H)-linked
methylglyoxal oxidoreductase |
Abstract |
Glutathione reductase (Glr1) activity controls cellular glutathione
and reactive oxygen species (ROS). We previously
demonstrated two predominant methylglyoxal scavengers–
NAD(H)-linked methylglyoxal oxidoreductase (Mgd1) and
alcohol dehydrogenase 1 (Adh1)–in glutathione-depleted γ-
glutamyl cysteinyl synthetase-disrupted Candida albicans.
However, experimental evidence for Candida pathophysiology
lacking the enzyme activities of Mgd1 and Adh1 on glutathione-
dependent redox regulation remains unclear. Herein,
we have aimed to demonstrate that glutathione-dependent
enzyme activities coupled with cellular ROS changes is regulated
by methylglyoxal accumulation in Δmgd1/Δadh1 double
disruptants. Δmgd1/Δadh1 showed severe growth defects
and G1-phase cell cycle arrest. The observed complementary
and reciprocal methylglyoxal-oxidizing and methylglyoxalreducing
activities between Δmgd1 and Δadh1 were not always
exhibited in Δmgd1/Δadh1. Although intracellular accumulation
of methylglyoxal and pyruvate was shown in all
disruptants, to a greater or lesser degree, methylglyoxal was
particularly accumulated in the Δmgd1/Δadh1 double disruptant.
While cellular ROS significantly increased in Δmgd1
and Δadh1 as compared to the wild-type, Δmgd1/Δadh1 underwent
a decrease in ROS in contrast to Δadh1. Despite the
experimental findings underlining the importance of the
undergoing unbalanced redox state of Δmgd1/Δadh1, glutathione-
independent antioxidative enzyme activities did not
change during proliferation and filamentation. Contrary to
the significantly lowered glutathione content and Glr1 enzyme
activity, the activity staining-based glutathione peroxidase
activities concomitantly increased in this mutant. Additionally,
the enhanced GLR1 transcript supported our results in
Δmgd1/Δadh1, indicating that deficiencies of both Adh1 and
Mgd1 activities stimulate specific glutathione-dependent enzyme
activities. This suggests that glutathione-dependent redox
regulation is evidently linked to C. albicans pathogenicity
under the control of methylglyoxal-scavenging activities. |