The ability of organisms to accommodate variations in metabolic need and environmental conditions is essential for their survival. However, an explanation is lacking as to how the necessary accommodations in response to these challenges are organized and coordinated from (sub)cellular to higher-level physiological functions, especially in mammals. We propose that the chemistry that enables coordination and synchronization of these processes dates to the origins of Life. We offer a conceptual framework based upon the nature of electron exchange (Redox) processes that co-evolved with biological complexification, giving rise to a multi-layered system in which intra/intercellular and inter-organ exchange processes essential to sensing and adaptation stay fully synchronized. Our analysis explains why Redox is both the lingua franca and the mechanism that enable integration by connecting the various elements of regulatory processes. We here define these interactions across levels of organization as the 'Redox Interactome'. This framework provides novel insight into the chemical and biological basis of Redox signalling and may explain the recent convergence of metabolism, bioenergetics, and inflammation as well as the relationship between Redox stress and human disease.