Prokaryotic Redox Switches

Abstract

Reduction-oxidation (redox) reactions are ubiquitous in metabolism. In microbial systems, individual cells monitor the internal and external environment with a diverse array of regulatory redox sensors that control the expression of appropriate adaptive responses. These sensors detect the presence of redox active molecules in the environment as well as those produced by metabolic processes within the cell. Molecular oxygen is the prototypic oxidant, and sensors of O₂ help coordinate the switch between anaerobic and aerobic lifestyles. The overall redox balance of the cell can be sensed by proteins monitoring the ratio of oxidized and reduced cofactors, such as low molecular weight thiols, the NADH pool, or membrane-associated quinones. Reactive oxygen and nitrogen species, produced endogenously or present in the environment, are also important signal molecules that can be readily sensed by their redox activity. This suite of sensor proteins is as diverse as their activating signals. Some sensors contain redox active metal centers that may include mononuclear iron, iron-sulfur clusters, and heme cofactors. Other redox switches rely on the facile oxidation and reduction of bound flavin cofactors or cysteine thiolates to effect changes in protein activity. Finally, some regulators assess redox-related signals by reversibly binding to molecules that signal redox status. A survey of these diverse mechanisms provides insights into the manifold pathways that enable cells to adapt to a range of environmental conditions that collectively comprise redox stress.