Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae

Darren Greetham, Jill Vickerstaff, Daniel Shenton, Gabriel G. Perrone, Ian W. Dawes, Chris M. Grant

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


Background: Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversibleoxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides withglutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulatingglutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be thepredominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins havegenerally been thought to be relatively inefficient in deglutathionylation.

Results: We show here that the levels of glutathionylated proteins in yeast are regulated in parallel with thegrowth cycle, and are maximal during stationary phase growth. This increase in glutathionylation is not a responseto increased reactive oxygen species generated from the shift to respiratory metabolism, but appears to be ageneral response to starvation conditions. Our data indicate that glutathionylation levels are constitutively high inall growth phases in thioredoxin mutants and are unaffected in glutaredoxin mutants. We have confirmed thatthioredoxins, but not glutaredoxins, catalyse deglutathionylation of model glutathionylated substrates usingpurified thioredoxin and glutaredoxin proteins. Furthermore, we show that the deglutathionylase activity ofthioredoxins is required to reduce the high levels of glutathionylation in stationary phase cells, which occurs ascells exit stationary phase and resume vegetative growth.

Conclusions: There is increasing evidence that the thioredoxin and glutathione redox systems have overlappingfunctions and these present data indicate that the thioredoxin system plays a key role in regulating themodification of proteins by the glutathione system.

Original languageEnglish
Article number3
Number of pages10
JournalBMC Biochemistry
Issue number1
Publication statusPublished - 14 Jan 2010
Externally publishedYes


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