Redox sensing: novel avenues and paradigms.

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.