An evolving understanding of the S-glutathionylation cycle in pathways of redox regulation.

By nature of the reversibility of the addition of glutathione to low pKa cysteine residues, the post-translational modification of S-glutathionylation sanctions a cycle that can create a conduit for cell signaling events linked with cellular exposure to oxidative or nitrosative stress. The modification can also avert proteolysis by protection from over-oxidation of those clusters of target proteins that are substrates. Altered functions are associated with S-glutathionylation of proteins within the mitochondria and endoplasmic reticulum compartments, and these impact energy production and protein folding pathways. The existence of human polymorphisms of enzymes involved in the cycle (particularly glutathione S-transferase P) create a scenario for inter-individual variance in response to oxidative stress and a number of human diseases with associated aberrant S-glutathionylation have now been identified.