Nonequilibrium thermodynamics of thiol/disulfide redox systems: A perspective on redox systems biology

• Type of Material: Article
• Authors: Melissa Lambeth Kemp, Emory University; Young-Mi Go, Emory University; Dean P Jones, Emory University
• Language: English
• Date: 2008-03-15
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.freeradbiomed.2007.11.008
• Title of Journal or Parent Work: Free Radical Biology and Medicine
• ISSN: 0891-5849
• Volume: 44
• Issue: 6
• Start Page: 921
• End Page: 937
• Grant/Funding Information: Research by the authors upon which this review was based was supported by NIH grants ES011195, ES009047, ES012929, and by support from the Whitaker Foundation.
• Keywords: Mitochondria; Glutathione; Endoplasmic reticulum; Nuclei, Cell; Systems biology; Oxidative stress; Thioredoxin; Reactive oxygen species; Redox signaling; Plasma; Cysteine; Kinetic analysis
• Research Categories: Biology, General; Health Sciences, General; Engineering, Biomedical

Abstract

Understanding the dynamics of redox elements in biologic systems remains a major challenge for redox signaling and oxidative stress research. Central redox elements include evolutionarily conserved subsets of cysteines and methionines of proteins which function as sulfur switches and labile reactive oxygen species (ROS) and reactive nitrogen species (RNS) which function in redox signaling. The sulfur switches depend upon redox environments in which rates of oxidation are balanced with rates of reduction through the thioredoxins, glutathione/glutathione disulfide and cysteine/cystine redox couples. These central couples, which we term redox control nodes, are maintained at stable but non-equilibrium steady states, are largely independently regulated in different subcellular compartments and are quasi-independent from each other within compartments. Disruption of the redox control nodes can differentially affect sulfur switches, thereby creating a diversity of oxidative stress responses. Systems biology provides approaches to address the complexity of these responses. In the present review, we summarize thiol/disulfide pathway, redox potential and rate information as a basis for kinetic modeling of sulfur switches. The summary identifies gaps in knowledge especially related to redox communication between compartments, definition of redox pathways and discrimination between types of sulfur switches. A formulation for kinetic modeling of GSH/GSSG redox control indicates that systems biology could encourage novel therapeutic approaches to protect against oxidative stress by identifying specific redox-sensitive sites which could be targeted for intervention.