The iron ion (Fe²⁺) effector pathway plays a critical role in iron acquisition and homeostasis, particularly under conditions where iron is limited or tightly sequestered in the environment. This pathway is regulated by IscR, a transcription factor that also functions as a sensor of iron-sulfur (Fe-S) cluster status within the cell. IscR adjusts gene expression in response to intracellular Fe²⁺ availability and Fe-S cluster demand. While IscR is primarily known for regulating Fe-S cluster biogenesis genes, it also contributes to broader iron homeostasis by modulating expression of iron transport systems, especially under iron-depleted or oxidative stress conditions. Key genes associated with the IscR regulog include the fbpABC operon, which encodes a high-affinity ferric iron (Fe³⁺) transport system that is functionally relevant when Fe²⁺ is oxidized or scarce: fbpA – Encodes a periplasmic iron-binding protein that captures ferric iron and delivers it to the membrane transport complex. fbpB – Encodes a membrane permease component of the transporter, forming a channel for iron translocation across the inner membrane. fbpC – Encodes an ATP-binding cassette (ABC) transporter ATPase, providing energy for active transport of iron into the cytoplasm. Together, these genes form the FbpABC transporter, a highly conserved system for iron import, particularly under iron-limiting conditions. Regulation by IscR allows the cell to integrate iron uptake with Fe-S cluster assembly and oxidative stress response, helping maintain iron homeostasis and protect against iron-mediated toxicity.

Iron ion, (Fe2+) References