The yeast glutaredoxins are active as glutathione peroxidases.
The yeast Saccharomyces cerevisiae contains two glutaredoxins, encoded by GRX1 and GRX2, which are active as glutathione-dependent oxidoreductases. Our studies show that changes in the levels of glutaredoxins affect the resistance of yeast cells to oxidative stress induced by hydroperoxides. Elevating the gene dosage of GRX1 or GRX2 increases resistance to hydroperoxides including hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide. The glutaredoxin-mediated resistance to hydroperoxides is dependent on the presence of an intact glutathione system, but does not require the activity of phospholipid hydroperoxide glutathione peroxidases (GPX1-3). Rather, the mechanism appears to be mediated via glutathione conjugation and removal from the cell because it is absent in strains lacking glutathione-S-transferases (GTT1, GTT2) or the GS-X pump (YCF1). We show that the yeast glutaredoxins can directly reduce hydroperoxides in a catalytic manner, using reducing power provided by NADPH, GSH, and glutathione reductase. With cumene hydroperoxide, high pressure liquid chromatography analysis confirmed the formation of the corresponding cumyl alcohol. We propose a model in which the glutathione peroxidase activity of glutaredoxins converts hydroperoxides to their corresponding alcohols; these can then be conjugated to GSH by glutathione-S-transferases and transported into the vacuole by Ycf1.
Collinson
Emma J
EJ
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, United Kingdom.
Wheeler
Glen L
GL
Garrido
Ester Ocón
EO
Avery
Angela M
AM
Avery
Simon V
SV
Grant
Chris M
CM
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000438:Alcohols / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000378:metabolism; D005838:Genotype; D054477:Glutaredoxins; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D010088:Oxidoreductases; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity
D018528:ATP-Binding Cassette Transporters; D000438:Alcohols; D001555:Benzene Derivatives; D005656:Fungal Proteins; D054477:Glutaredoxins; D011506:Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; C007164:cumene hydroperoxide; D010100:Oxygen