The reactive species interactome

Abstract Enzymatically generated reactive species are emerging as endogenous signaling molecules, targeting specific thiol/metal redox switches in proteins and organelles, thereby affecting cell metabolism and survival. To better characterize the complex network of interactions of reactive species with themselves and their biological targets and to understand their significance for metabolic control, we recently introduced the “reactive species interactome” (RSI) concept. The RSI is a primeval redox system that connects the (bio)chemical pathways that generate reactive species with cellular intermediary metabolism, bioenergetics, and the extracellular environment. The main characteristics of the RSI are (a) robustness and flexibility, (b) adaptability and rapid responsiveness, and (c) the ability to sense the chemical composition of intra- and extracellular milieu. These properties enable cells/organs to communicate and sense and adapt to changes in environmental conditions and metabolic demand. As conceptual framework, the RSI may enable to better understand how complex life forms operate and respond to challenges at the whole organism level, potentially enabling us to harness this information for medical use in health and disease.