title: S-glutathionylation: from molecular mechanisms to health outcomes.
abstract: Redox homeostasis governs a number of critical cellular processes. In turn, imbalances in pathways that control oxidative and reductive conditions have been linked to a number of human disease pathologies, particularly those associated with aging. Reduced glutathione is the most prevalent biological thiol and plays a crucial role in maintaining a reduced intracellular environment. Exposure to reactive oxygen or nitrogen species is causatively linked to the disease pathologies associated with redox imbalance. In particular, reactive oxygen species can differentially oxidize certain cysteine residues in target proteins and the reversible process of S-glutathionylation may mitigate or mediate the damage. This post-translational modification adds a tripeptide and a net negative charge that can lead to distinct structural and functional changes in the target protein. Because it is reversible, S-glutathionylation has the potential to act as a biological switch and to be integral in a number of critical oxidative signaling events. The present review provides a comprehensive account of how the S-glutathionylation cycle influences protein structure/function and cellular regulatory events, and how these may impact on human diseases. By understanding the components of this cycle, there should be opportunities to intervene in stress- and aging-related pathologies, perhaps through prevention and diagnostic and therapeutic platforms.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, 29425, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.forename: Joachim D
authors.initials: JD
authors.lastname: Uys
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tew
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009422:Nervous System Diseases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione