Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide.
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Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide. / López-Mirabal, H Reynaldo; Thorsen, Michael; Kielland-Brandt, Morten C; Toledano, Michel B; Winther, Jakob R.
I: FEMS Yeast Research, Bind 7, Nr. 3, 2007, s. 391-403.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide.
AU - López-Mirabal, H Reynaldo
AU - Thorsen, Michael
AU - Kielland-Brandt, Morten C
AU - Toledano, Michel B
AU - Winther, Jakob R
N1 - Keywords: Disulfides; Glutamate-Cysteine Ligase; Glutathione; Glutathione Disulfide; Membrane Proteins; Mutagenesis, Insertional; Oxidation-Reduction; Plasmids; Pyridines; Receptors, Peptide; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sulfhydryl Reagents; Superoxide Dismutase; Thioredoxins; Transcription Factors
PY - 2007
Y1 - 2007
N2 - Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-cysteine synthetase) and, particularly, GLR1 (glutathione reductase) are required for survival on DPS. DPS is uniquely thiol-specific, and we found that the cellular mechanisms for DPS detoxification differ substantially from that of the commonly used thiol oxidant diamide. In contrast to this oxidant, the full antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS sensitivity. DPS seems to induce a specific disulfide stress, where an increase in the cytoplasmic/nuclear GSSG/GSH ratio results in putative DPS target(s) becoming sensitive to DPS. Udgivelsesdato: 2007-May
AB - Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-cysteine synthetase) and, particularly, GLR1 (glutathione reductase) are required for survival on DPS. DPS is uniquely thiol-specific, and we found that the cellular mechanisms for DPS detoxification differ substantially from that of the commonly used thiol oxidant diamide. In contrast to this oxidant, the full antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS sensitivity. DPS seems to induce a specific disulfide stress, where an increase in the cytoplasmic/nuclear GSSG/GSH ratio results in putative DPS target(s) becoming sensitive to DPS. Udgivelsesdato: 2007-May
U2 - 10.1111/j.1567-1364.2006.00202.x
DO - 10.1111/j.1567-1364.2006.00202.x
M3 - Journal article
C2 - 17253982
VL - 7
SP - 391
EP - 403
JO - FEMS Yeast Research
JF - FEMS Yeast Research
SN - 1567-1356
IS - 3
ER -
ID: 3090477