Protein S-glutathionylation and the regulation of cellular functions

Abstract Protein S-glutathionylation is a ubiquitous and reversible posttranslation modification that involves the addition and removal of GSH to and from a protein cysteine thiol. These reactions are catalyzed by glutaredoxins (GRX), thiol oxidoreductases that S-glutathionylate and deglutathionylate target proteins in response to fluctuations in the redox state of cellular glutathione pools. The modification of proteins with GSH modulates a number cell functions in response to environmental and physiological cues including energy metabolism and sensing, apoptosis, calcium handling, signaling, and protein folding. Protein S-glutathionylation also serves as a superimposed cosignal that works in tandem with other pathways to regulate cell functions. Here, we discuss the various ways that protein S-glutathionylation serves as one of the main devices for the regulation of various cell proteins during oxidative eustress signaling.