title: The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.
abstract: CONCLUSIONS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Cardiovascular Research Laboratory, Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University , Düsseldorf, Germany .
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Cortese-Krott
authors.affiliation: 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Anne
authors.initials: A
authors.lastname: Koning
authors.affiliation: 3 Department of Food and Nutritional Sciences, University of Reading , Reading, United Kingdom .
authors.forename: Gunter G C
authors.initials: GGC
authors.lastname: Kuhnle
authors.affiliation: 4 Molecular Immunology and Toxicology, National Institute of Oncology , Budapest, Hungary .
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: 5 Department of Chemistry, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bianco
authors.affiliation: 6 Department of Clinical Chemistry, University of Bern and Calciscon AG , Bern, Switzerland .
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
authors.affiliation: 7 Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health , Frederick, Maryland.
authors.forename: David A
authors.initials: DA
authors.lastname: Wink
authors.affiliation: 8 Department of Chemistry, Sonoma State University , Rohnert Park, California.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
authors.affiliation: 9 NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom .
authors.forename: Alan A
authors.initials: AA
authors.lastname: Jackson
authors.affiliation: 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: 10 Indiana University School of Medicine-South Bend , South Bend, Indiana.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Olson
authors.affiliation: 9 NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom .|11 Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital and Institute for Life Sciences, University of Southampton , Southampton, United Kingdom .
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods*; D010084:Oxidation-Reduction; D057285:Precision Medicine; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013440:Sulfides; D006862:Hydrogen Sulfide
keywords: hydrogen sulfide; microbiome; network medicine; nitric oxide; polysulfides; systems biology