Protein S -glutathiolation: Redox-sensitive regulation of protein function

• Published in: Journal of molecular and cellular cardiology Vol. 52; no. 3; pp. 559 - 567
• Main Authors: Hill, Bradford G, Bhatnagar, Aruni
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2012
• Subjects: Animals; Cardiovascular; Glutathione - metabolism; Glutathione Disulfide - metabolism; Glutathionylation; Heart; Humans; Nitric oxide; Oxidation-Reduction; Oxidative Stress; Protein Processing, Post-Translational; Protein-mixed disulfides; Proteins - metabolism; Signal Transduction; Vasculature; Heart; Oxidative stress; Glutathionylation; Protein-mixed disulfides; Nitric oxide; Vasculature
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2011.07.009

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.”