sglutathionylated

S-glutathionylation is a reversible post-translational modification in which a glutathione molecule forms a mixed disulfide with a protein cysteine residue, yielding a protein–S–S–G moiety. This modification occurs under conditions of oxidative or nitrosative stress, but it can also participate in normal redox signaling. It can protect sensitive cysteines from irreversible overoxidation and simultaneously serve as a reversible switch for protein function and activity.

Mechanism and reversal: The reactive thiol of a cysteine can be oxidized by reactive oxygen or nitrogen species to a sulfenic acid, which can react with reduced glutathione to form the mixed disulfide, R-S-S-G. Direct formation with GSSG can also produce the same product. The modification is typically reversible; non-enzymatic processes and enzymatic systems contribute to its formation and removal. Deglutathionylation is mainly driven by glutaredoxins (such as Grx1 and Grx2) using the cellular reducing pool, though the thioredoxin system can also participate in reversal.

Biological significance: S-glutathionylation modulates the activity, stability, or localization of target proteins, influencing metabolism, cytoskeletal dynamics, and signaling pathways. It acts as a protective mechanism to preserve cysteine function under oxidative stress and as a regulatory redox switch in signaling networks. Abnormal glutathionylation has been linked to aging and various diseases associated with oxidative stress.

Detection and context: Proteomics and redox biology methods identify glutathionylated cysteines in proteins, often using mass spectrometry or specific antibodies, and exploit the reversible nature by applying reducing conditions to demonstrate loss of modification. The term S-glutathionylated describes a protein in this modified state.