Microbial H2O2 sensors as archetypical redox signaling modules.

The Saccharomyces cerevisiae Orp1–Yap1 sensor and its prokaryotic counterpart OxyR are master regulators of cellular H2O2 homeostasis. These sensors share a stereotypical mechanism, involving the reaction of a unique cysteine with H2O2 and a physiology coupled to metabolism of H2O2 and thiol reduction–oxidation (redox). However they differ fundamentally in their core mechanism. Whereas OxyR carries out both sensing and transcriptional regulatory functions, these functions are dissociated in yeast, where Orp1 senses H2O2 and converts this signal into a cysteine-based redox cascade that culminates in oxidation of the Yap1 regulator. We propose a model in which H2O2 sensors are viewed as archetypical receptor-initiated redox signaling modules and suggest, on the basis of the high specificity of the H2O2-sensing mechanism, that kinetic factors rather than thermodynamics define the cellular pathways of cysteine residue oxidation.