Many roles of the bacterial envelope reducing pathways.

SIGNIFICANCE: The cell envelope of aerobic bacteria is an oxidizing environment in which most cysteine residues are involved in disulfide bonds. However, reducing redox pathways are also present in this cellular compartment where they provide electrons to a variety of cellular processes. The membrane protein DsbD plays a central role in these pathways by functioning as an electron hub that dispatches electrons received from the cytoplasmic thioredoxin system to periplasmic oxidoreductases. RECENT ADVANCES: Recent data have revealed that DsbD provides reducing equivalents to a large array of periplasmic redox proteins. Those proteins use the reducing power received from DsbD to correct non-native disulfides, mature c-type cytochromes, protect cysteines on secreted proteins from irreversible oxidation, reduce methionine sulfoxides, and scavenge reactive oxygen species such as hydrogen peroxide. CRITICAL ISSUES: Despite the prominent role played by DsbD, we have a poor understanding of how this protein transfers electrons across the inner membrane. Another critical issue will be to grasp the full physiological significance of the new reducing pathways that have been identified in the cell envelope such as the peroxide reduction pathway. FUTURE DIRECTIONS: A detailed understanding of DsbD's mechanism will require solving the structure of this intriguing protein. Moreover, bioinformatic, biochemical, and genetic approaches need to be combined for a better comprehension of the broad spectrum of periplasmic reducing systems present in bacteria, which will likely lead to the discovery of novel pathways.