title: Protein S-glutathiolation: redox-sensitive regulation of protein function.
abstract: Reversible protein S-glutathiolation has emerged as an important mechanism of post-translational modification. Under basal conditions several proteins remain adducted to glutathione, and physiological glutathiolation of proteins has been shown to regulate protein function. Enzymes that promote glutathiolation (e.g., glutathione-S-transferase-P) or those that remove glutathione from proteins (e.g., glutaredoxin) have been identified. Modification by glutathione has been shown to affect protein catalysis, ligand binding, oligomerization and protein-protein interactions. Conditions associated with oxidative or nitrosative stress, such as ischemia-reperfusion, hypertension and tachycardia increase protein glutathiolation via changes in the glutathione redox status (GSH/GSSG) or through the formation of sulfenic acid (SOH) or nitrosated (SNO) cysteine intermediates. These "activated" thiols promote reversible S-glutathiolation of key proteins involved in cell signaling, energy production, ion transport, and cell death. Hence, S-glutathiolation is ideally suited for integrating and mounting fine-tuned responses to changes in the redox state. S-glutathiolation also provides a temporary glutathione "cap" to protect protein thiols from irreversible oxidation and it could be an important mechanism of protein "encryption" to maintain proteins in a functionally silent state until they are needed during conditions of stress. Current evidence suggests that the glutathiolation-deglutathiolation cycle integrates and interacts with other post-translational mechanisms to regulate signal transduction, metabolism, inflammation, and apoptosis. This article is part of a Special Section entitled "Post-translational Modification."
authors.affiliation: Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Hill
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011506:Proteins; D005978:Glutathione; D019803:Glutathione Disulfide