Disruption of γ-glutamylcysteine synthetase results in absolute glutathione auxotrophy and apoptosis in Candida albicans

被引:50
作者
Baek, YU
Kim, YR
Yim, HS [1 ]
Kang, SO
机构
[1] Seoul Natl Univ, Sch Biol Sci, Biophys Lab, Seoul 151742, South Korea
[2] Seoul Natl Univ, Inst Microbiol, Seoul 151742, South Korea
关键词
glutathione; gamma-glutamylcysteine synthetase; apoptosis; Candida albicans;
D O I
10.1016/S0014-5793(03)01363-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glutathione is the most abundant non-protein thiol and a major source of reducing equivalents in eukaryotes. We examined the role of glutathione in Candida albicans by the disruption of gamma-glutamylcysteine synthetase (GCS1), an essential enzyme in glutathione biosynthesis. The gcs1lgcs1 null mutants exhibited glutathione auxotrophy, which could be rescued by supplementing with reduced and oxidized glutathione and gamma-glutamylcysteine. When the mutants were depleted of glutathione, they showed typical markers of apoptosis. These results suggest that glutathione itself is an essential metabolite and C. albicans lacking GCS1 undergoes apoptosis. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:47 / 52
页数:6
相关论文
共 38 条
[1]   ISOLATION AND INITIAL CHARACTERIZATION OF GLUTATHIONE-DEFICIENT MUTANTS OF ESCHERICHIA-COLI K-12 [J].
APONTOWEIL, P ;
BERENDS, W .
BIOCHIMICA ET BIOPHYSICA ACTA, 1975, 399 (01) :10-22
[2]   Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line [J].
Armstrong, JS ;
Steinauer, KK ;
Hornung, B ;
Irish, JM ;
Lecane, P ;
Birrell, GW ;
Peehl, DM ;
Knox, SJ .
CELL DEATH AND DIFFERENTIATION, 2002, 9 (03) :252-263
[3]   Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress [J].
Carmel-Harel, O ;
Storz, G .
ANNUAL REVIEW OF MICROBIOLOGY, 2000, 54 :439-461
[4]  
Chaudhuri B, 1997, GENETICS, V145, P75
[5]   PUTATIVE VIRULENCE FACTORS OF CANDIDA-ALBICANS [J].
CUTLER, JE .
ANNUAL REVIEW OF MICROBIOLOGY, 1991, 45 :187-218
[6]   Cell cycle and morphological alterations as indicative of apoptosis promoted by UV irradiation in S-cerevisiae [J].
Del Carratore, R ;
Della Croce, C ;
Simili, M ;
Taccini, E ;
Scavuzzo, M ;
Sbrana, S .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2002, 513 (1-2) :183-191
[7]   Ras signaling is required for serum-induced hyphal differentiation in Candida albicans [J].
Feng, QH ;
Summers, E ;
Guo, B ;
Fink, G .
JOURNAL OF BACTERIOLOGY, 1999, 181 (20) :6339-6346
[8]   Cell signalling and the glutathione redox system [J].
Filomeni, G ;
Rotilio, G ;
Ciriolo, MR .
BIOCHEMICAL PHARMACOLOGY, 2002, 64 (5-6) :1057-1064
[9]   Oxidants, oxidative stress and the biology of ageing [J].
Finkel, T ;
Holbrook, NJ .
NATURE, 2000, 408 (6809) :239-247
[10]   Mitochondrial reactive oxygen species in cell death signaling [J].
Fleury, C ;
Mignotte, B ;
Vayssière, JL .
BIOCHIMIE, 2002, 84 (2-3) :131-141