Disruption of gamma-glutamylcysteine synthetase results in absolute glutathione auxotrophy and apoptosis in Candida albicans.
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 gcs1/gcs1 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.
Baek
Yong-Un
YU
Laboratory of Biophysics, School of Biological Sciences, and Institute of Microbiology, Seoul National University, 151-742, Seoul, South Korea.
Kim
Yeon-Ran
YR
Yim
Hyung-Soon
HS
Kang
Sa-Ouk
SO
D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D053938:DNA Fragmentation; D005434:Flow Cytometry; D017353:Gene Deletion; D005721:Glutamate-Cysteine Ligase / Q000235:genetics* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D015415:Biomarkers; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione