The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.
- Cortese-Krott MM 1 Cardiovascular Research Laboratory, Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University , Düsseldorf, Germany .
- Koning A 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
- Kuhnle GGC 3 Department of Food and Nutritional Sciences, University of Reading , Reading, United Kingdom .
- Nagy P 4 Molecular Immunology and Toxicology, National Institute of Oncology , Budapest, Hungary .
- Bianco CL 5 Department of Chemistry, Johns Hopkins University , Baltimore, Maryland.
- Pasch A 6 Department of Clinical Chemistry, University of Bern and Calciscon AG , Bern, Switzerland .
- Wink DA 7 Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health , Frederick, Maryland.
- Fukuto JM 8 Department of Chemistry, Sonoma State University , Rohnert Park, California.
- Jackson AA 9 NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom .
- van Goor H 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
- Olson KR 10 Indiana University School of Medicine-South Bend , South Bend, Indiana.
- Feelisch M 9 NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom .
- 2017-04-12
Published in:
- Antioxidants & redox signaling. - 2017
hydrogen sulfide
microbiome
network medicine
nitric oxide
polysulfides
systems biology
Adaptation, Physiological
Animals
Humans
Hydrogen Sulfide
Metabolomics
Oxidation-Reduction
Precision Medicine
Reactive Nitrogen Species
Reactive Oxygen Species
Sulfides
English
SIGNIFICANCE
Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level.
CRITICAL ISSUES
To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses.
FUTURE DIRECTIONS
Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.
Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level.
CRITICAL ISSUES
To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses.
FUTURE DIRECTIONS
Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1089/ars.2017.7083
- PMID 28398072
- Persistent URL
- https://sonar.ch/global/documents/206054
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