The Chemical Biology of Cellular Iron Pools in Prokaryotes

Mobilization and trafficking of intracellular iron pools for metallocafactor biogenesis requires that iron be directed into the most essential pathways to maintain cell viability and growth. This process is complicated by the large number of iron‐containing metalloproteins that use a variety of iron cofactors such as mono‐ and di‐nuclear iron centers, heme, and iron‐sulfur (Fe‐S) clusters. In many cases there are competing requirements for iron to be used for multiple iron metalloproteins to ensure proper function of critical processes, such as central carbon metabolism. Intracellular iron homeostasis is also sensitive to disruption by reactive oxygen species, iron starvation, and other stresses. Using a combination of genetic, biochemical, and spectroscopic approaches, we have begun to establish the relative roles of different iron storage proteins (FtnA, FtnB, Bfr, and Dps) as sources of intracellular iron for Fe‐S cluster biogenesis by the Suf system. The Suf pathway is a stress‐responsive Fe‐S cluster biogenesis system in E. coli that must acquire iron and maintain Fe‐S cluster assembly during oxidative stress and iron starvation. Our initial results indicate that Suf accesses specific pools of intracellular stored and labile iron. We have also discovered that deletion of the various iron storage proteins alters existing pools of iron in the cell. These studies have begun to unravel the complexities of intracellular redistribution of iron during stress conditions.Overview of intracellular iron pools in E. coli and their interactions with iron storage, iron metalloregulatory, and iron cofactor biogenesis systems.