Redox-based transcriptional regulation in prokaryotes: revisiting model mechanisms.

Significance: The successful adaptation of microorganisms to ever-changing environments depends, to a great extent, on their ability to maintain redox homeostasis. To effectively maintain the redox balance, cells have developed a variety of strategies mainly coordinated by a battery of transcriptional regulators through diverse mechanisms. Recent Advances: This comprehensive review focuses on the main mechanisms used by major redox-responsive regulators in prokaryotes and their relationship with the different redox signals received by the cell. An overview of the corresponding regulons is also provided. Critical Issues: Some regulators are difficult to classify since they may contain several sensing domains and respond to more than one signal. We propose a classification of redox-sensing regulators into three major groups. The first group contains one-component or direct regulators, whose sensing and regulatory domains are in the same protein. The second group comprises the classical two-component systems involving a sensor kinase that transduces the redox signal to its DNA-binding partner. The third group encompasses a heterogeneous group of flavin-based photosensors whose mechanisms are not always fully understood and are often involved in more complex regulatory networks. Future Directions: Redox-responsive transcriptional regulation is an intricate process as identical signals may be sensed and transduced by different transcription factors, which often interplay with other DNA-binding proteins with or without regulatory activity. Although there is much information about some key regulators, many others remain to be fully characterized due to the instability of their clusters under oxygen. Understanding the mechanisms and the regulatory networks operated by these regulators is essential for the development of future applications in biotechnology and medicine.