The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

Miriam M. Cortese-Krott, Anne Koning, Gunter G.C. Kuhnle, Peter Nagy, Christopher L. Bianco, Andreas Pasch, David A. Wink, Jon M. Fukuto, Alan A. Jackson, Harry Van Goor, Kenneth R. Olson, Martin Feelisch

Research output: Contribution to journalReview article

59 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)684-712
Number of pages29
JournalAntioxidants and Redox Signaling
Issue number10
StatePublished - Oct 1 2017



  • hydrogen sulfide
  • microbiome
  • network medicine
  • nitric oxide
  • polysulfides
  • systems biology

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Cortese-Krott, M. M., Koning, A., Kuhnle, G. G. C., Nagy, P., Bianco, C. L., Pasch, A., Wink, D. A., Fukuto, J. M., Jackson, A. A., Van Goor, H., Olson, K. R., & Feelisch, M. (2017). The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine. Antioxidants and Redox Signaling, 27(10), 684-712.