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Redox Systems Biology: Harnessing the Sentinels of the Cysteine Redoxome.

Authors
  • Held, Jason M1, 2, 3
  • 1 Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
  • 2 Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
  • 3 Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Type
Published Article
Journal
Antioxidants & Redox Signaling
Publisher
Mary Ann Liebert
Publication Date
Apr 01, 2020
Volume
32
Issue
10
Pages
659–676
Identifiers
DOI: 10.1089/ars.2019.7725
PMID: 31368359
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Significance: Cellular redox processes are highly interconnected, yet not in equilibrium, and governed by a wide range of biochemical parameters. Technological advances continue refining how specific redox processes are regulated, but broad understanding of the dynamic interconnectivity between cellular redox modules remains limited. Systems biology investigates multiple components in complex environments and can provide integrative insights into the multifaceted cellular redox state. This review describes the state of the art in redox systems biology as well as provides an updated perspective and practical guide for harnessing thousands of cysteine sensors in the redoxome for multiparameter characterization of cellular redox networks. Recent Advances: Redox systems biology has been applied to genome-scale models and large public datasets, challenged common conceptions, and provided new insights that complement reductionist approaches. Advances in public knowledge and user-friendly tools for proteome-wide annotation of cysteine sentinels can now leverage cysteine redox proteomics datasets to provide spatial, functional, and protein structural information. Critical Issues: Careful consideration of available analytical approaches is needed to broadly characterize the systems-level properties of redox signaling networks and be experimentally feasible. The cysteine redoxome is an informative focal point since it integrates many aspects of redox biology. The mechanisms and redox modules governing cysteine redox regulation, cysteine oxidation assays, proteome-wide annotation of the biophysical and biochemical properties of individual cysteines, and their clinical application are discussed. Future Directions: Investigating the cysteine redoxome at a systems level will uncover new insights into the mechanisms of selectivity and context dependence of redox signaling networks.

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