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Open Access Highly Accessed Research article

Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae

Darren Greetham1, Jill Vickerstaff1, Daniel Shenton1, Gabriel G Perrone12, Ian W Dawes12 and Chris M Grant1*

Author Affiliations

1 The University of Manchester, Faculty of Life Sciences, Manchester M13 9PT, UK

2 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia

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BMC Biochemistry 2010, 11:3  doi:10.1186/1471-2091-11-3

Published: 14 January 2010

Abstract

Background

Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally 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 the growth cycle, and are maximal during stationary phase growth. This increase in glutathionylation is not a response to increased reactive oxygen species generated from the shift to respiratory metabolism, but appears to be a general response to starvation conditions. Our data indicate that glutathionylation levels are constitutively high in all growth phases in thioredoxin mutants and are unaffected in glutaredoxin mutants. We have confirmed that thioredoxins, but not glutaredoxins, catalyse deglutathionylation of model glutathionylated substrates using purified thioredoxin and glutaredoxin proteins. Furthermore, we show that the deglutathionylase activity of thioredoxins is required to reduce the high levels of glutathionylation in stationary phase cells, which occurs as cells exit stationary phase and resume vegetative growth.

Conclusions

There is increasing evidence that the thioredoxin and glutathione redox systems have overlapping functions and these present data indicate that the thioredoxin system plays a key role in regulating the modification of proteins by the glutathione system.