S-Space College of Natural Sciences (자연과학대학) Dept. of Biological Sciences (생명과학부) Theses (Ph.D. / Sc.D._생명과학부)
Role of glutathione reductase in the differentiation of Candida albicans
Candida albicans의 분화에서 glutathione reductase의 역할
- 자연과학대학 생명과학부
- Issue Date
- 서울대학교 대학원
- Glutathione reductase; glutathione; methylglyoxal; fructose-1; 6-bisphosphate aldolase; Efg1-mediated cyclic AMP/protein kinase A pathways; Candida albicans
- 학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 강사욱.
- Glutathione reductase adequately maintains the glutathione level in a reduced state to regulate redox state. It was evidently confirmed that glutathione is required for cell growth and division, and its biosynthesizing-enzyme deficiency causes methylglyoxal accumulation. However, experimental evidence for reciprocal relationships between Cph1-/Efg1-mediated signaling pathway regulation and methylglyoxal production exerted from glycolysis pathway by glutathione reductase on yeast morphology, and the origin of methylglyoxal production remain unclear.
In this study, glutathione reductase (GLR1) mutants were used to examine aspects of pathological and morphological alterations in Candida albicans. These were proved by observations of cellular susceptibility to oxidants and thiols, and measurements of methylglyoxal, reactive oxygen species and glutathione content in hyphal-inducing conditions mainly through the activity of GLR1-overexpressing cells. Additionally, the transcriptional and translational levels of bioenergetic enzymes and dimorphism-regulating protein kinases were examined in the strain.
As expected, the GLR1-deficient strain was non-viable when GLR1 expression under the control of a CaMAL2 promoter was conditionally repressed even with various exogenous thiols. During filamentation, GLR1-overexpressing cells displayed non-hyphal growth and exhibited resistance against oxidants and the cellular methylglyoxal decrease significantly, which concomitantly increased expressions of genes encoding bioenergetic enzymes, including fructose-1,6-bisphosphate aldolase (FBA1), glyceraldehyde-3-phosphate dehydrogenase (TDH3), and alcohol dehydrogenase (ADH1), with remarkable repression of Efg1-signaling cascades.
Herein, GLR1 repressed Efg1-mediated signal transduction strictly to reduce morphological switching and virulence by maintaining the basal level of methylglyoxal following the high gene expressions of glycolytic enzymes and ADH1. The Efg1-mediated down-regulatory mechanism by GLR1 expression has possibilities to involve in other complex networks of signal pathways, especially glycolysis.