The regulation of iron transport

Iron is an essential nutrient, but its concentration and distribution in the body must be tightly controlled due to its inherent toxicity and insolubility in aqueous solution. Living systems have successfully overcome these potential limitations by evolving a range of iron binding proteins and transport systems that effectively maintain iron in a nontoxic and soluble form for much, if not all, of its time within the body. In the circulation, iron is transported to target organs bound to the serum iron binding protein transferrin. Individual cells modulate their uptake of transferrin-bound iron depending on their iron requirements, using both transferrin receptor 1-dependent and independent pathways. Once inside the cell, iron can be chaperoned to sites of need or, if in excess, stored within ferritin. Iron is released from cells by the iron export protein ferroportin1, which requires the ferroxidase activity of ceruloplasmin or hephestin to load iron safely onto transferrin. The regulation of iron export is controlled predominantly at the systemic level by the master regulator of iron homeostasis hepcidin. Hepcidin, in turn, responds to changes in body iron demand, making use of a range of regulatory mechanisms that center on the bone morphogenetic protein signaling pathway. This review provides an overview of recent advances in the field of iron metabolism and outlines the key components of the iron transport and regulation systems.