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Author Notes:

Correspondence: Dr. Dean P. Jones, 205 Whitehead Research Center, Emory University, Atlanta, GA 30322; Phone: 404-727-5970; Fax: 404-712-2974; Email: dpjones@emory.edu

Subjects:

Research Funding:

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:

  • Thioredoxin
  • Glutathione
  • Cysteine
  • Mitochondria
  • Nuclei, Cell
  • Endoplasmic reticulum
  • Plasma
  • Systems biology
  • Oxidative stress
  • Redox signaling
  • Reactive oxygen species
  • Kinetic analysis

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

Tools:

Journal Title:

Free Radical Biology and Medicine

Volume:

Volume 44, Number 6

Publisher:

, Pages 921-937

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2007 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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