CHAPTER 6. Nonhaem Iron-based Sensors of Reactive Oxygen and Nitrogen Species

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are constitutively generated in biological systems as side-products of oxidation reactions. Due to their high chemical reactivity, many organisms have developed effective elimination and defence systems for ROS and RNS. Although ROS and RNS are harmful nuisances for cells, the amount of ROS and RNS depends on the oxidation states and redox status of cells, and these reactive species can be utilized as the signalling molecules for adaptive response to the oxidative stress and unusual redox balance. All organisms from bacterial to mammalian, therefore, have specific sensing systems for ROS and RNS to promote survival. In addition, ROS and RNS are intentionally generated by specific enzymes under cellular control, which can serve as effective chemical weapons against invading pathogens. Hosts fight pathogens by generating ROS and RNS as the chemical weapons, while pathogens defend the attack of ROS and RNS by sensing them and activating their defence system. Although all of the cell components are targets of ROS and RNS, the iron ions are highly susceptible to ROS and RNS. Consequently, these ions are widely used as the active centres for sensing ROS and RNS. Binding of ROS or RNS to nonhaem iron-based sensors initiates specific responses such as expression of genes encoding enzymes in elimination and defence systems for ROS and RNS. In this chapter, several nonhaem iron-based sensors showing unique sensing mechanisms are reviewed, focusing on their molecular structure and reaction mechanisms for sensing ROS and RNS, as well as the biological significance of these reactive species.