Redox Sensing: Novel Avenues and Paradigms

Abstract

The response to changes in the redox state of the cell environment is closely coupled with the ability of living organisms to sense changing conditions. Protein-based redox sensors utilize cofactors, that is, iron–sulfur clusters, flavins, or hemes, for environmental sensing. Under oxidizing conditions a cofactor-mediated post-translational modification (i.e., thiol-oxidation, carbonylation, or dityrosine formation) accompanied by a structural change in the protein occurs that results in an appropriate reaction, mostly in terms of expression of genes involved in antioxidative stress responses. In addition to these well-studied cofactors, researchers have recently discovered and described redox-active metabolites that play a role in redox sensing. Furthermore, not only proteins but also nucleic acids are able to sense redox-stressing events and to elucidate the corresponding response. With these all sensors, organisms are well equipped to sense redox-stress signals generated extracellularly as well as cytoplasmatically. To analyze the molecular mechanisms of all these redox sensors as well as to describe the paradigms involved, a number of sophisticated tools have been applied. These include development of novel protein fluorescence resonance energy transfer probes to microscopically analyze redox signaling in cells or the application of X-ray crystallography combined with spectroscopic studies to monitor dynamics of conformational changes within redox sensors. In this Forum, novel redox-sensing systems, novel avenues, and recent technical advances in the emerging field of redox sensing are presented. Antioxid. Redox Signal. 16, 636–638.