Novel redox-sensing modules: accessory protein- and nucleic acid-mediated signaling.

SIGNIFICANCE: Organisms have evolved both enzymatic and nonenzymatic pathways to prevent oxidative damage to essential macromolecules, including proteins and nucleic acids. Pathways modulated by different protein-based sensory and regulatory modules ensure a rapid and appropriate response. RECENT ADVANCES: In contrast to classical two-component systems that possess internal sensory and regulatory modules, an accessory protein-dependent redox-signaling system has been recently characterized in bacteria. This system senses extracellular iron-mediated oxidative stress signals via an extracellularly located protein (HbpS). In vivo and in vitro studies allowed the elucidation of molecular mechanisms governing this system. Moreover, recent studies show that nucleic acids may also participate in redox-signaling during antioxidative stress response. CRITICAL ISSUES: Research for novel redox-signaling systems is often focused on known types of sensory and regulatory modules. It is also often considered that the oxidative attack of macromolecules, leading to modification and degradation processes, is the final step during oxidative stress. However, recent studies have demonstrated that oxidatively modified macromolecules can be intermediary states in the process of redox-signaling. FUTURE DIRECTIONS: Analyses of adjacent regions of genes encoding for known sensory and regulatory modules can identify potential accessory modules that may increase the complexity of sensing systems. Despite the fact that the involvement of DNA-mediated signaling in the modulation of one bacterial regulator protein has been analyzed in detail, further studies are necessary to identify additional regulators. Given the role of DNA in oxidative-stress response, it is tempting to hypothesize that RNA modules may also mediate redox-signaling.