Ferritin as an Iron Concentrator and Chelator Target

A bstract : Ferritin has a broad role to play in new strategies for managing Cooley's anemia and the thalassemias. Serum ferritin iron content is relegated to reporting on tissue iron concentrations. Recently, a new property of ferritin was discovered: gated pores, which are highly conserved in ferritins of humans down to bacteria, and control iron flow to chelators. The pore gates can be selectively opened to increase chelator access by mutation, temperature, and physiological concentrations of urea. In another recent observation, the iron in ferritin from seeds such as soybeans has been shown to be readily available to tissues with high demand for iron, such as red blood cells, but slower to be mobilized in other tissues, compared to nonheme iron salts, presumably through a controlled iron gating mechanism. Because the iron pore gating property of ferritin is more thoroughly investigated, and the knowledge that much of the iron to be chelated in the thalassemias is from a solid iron mineral inside the ferritin protein nanocage, a new role of ferritin in regulating cellular iron homeostasis is established. Two new areas, based on recent knowledge of the molecular properties of ferritin, are (1) exploration of food ferritin as a potentially safer form of dietary nonheme iron, and (2) development of chelators targeted to ferritin protein pores that control chelator access.