TY - JOUR
T1 - The Reactive Species Interactome
T2 - Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine
AU - Cortese-Krott, Miriam M.
AU - Koning, Anne
AU - Kuhnle, Gunter G. C.
AU - Nagy, Peter
AU - Bianco, Christopher L.
AU - Pasch, Andreas
AU - Wink, David A.
AU - Fukuto, Jon M.
AU - Jackson, Alan A.
AU - van Goor, Harry
AU - Olson, Kenneth R.
AU - Feelisch, Martin
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - hydrogen sulfide
KW - polysulfides
KW - nitric oxide
KW - systems biology
KW - microbiome
KW - network medicine
KW - CELLULAR STRESS-RESPONSE
KW - NITRIC-OXIDE SYNTHESIS
KW - CORONARY-ARTERY-DISEASE
KW - AMINO-ACID-METABOLISM
KW - HYDROGEN-SULFIDE
KW - OXIDATIVE STRESS
KW - CHEMICAL BIOLOGY
KW - CROSS-TALK
KW - IN-VIVO
KW - SUPEROXIDE DISMUTASES
U2 - 10.1089/ars.2017.7083
DO - 10.1089/ars.2017.7083
M3 - Review article
VL - 27
SP - 684
EP - 712
JO - Antioxidants & Redox Signaling
JF - Antioxidants & Redox Signaling
SN - 1523-0864
IS - 10
ER -