The ferroxidase–permease system for transport of iron across membranes: from yeast to humans

Transport of iron across the cell membrane is a tightly controlled process carried out by specific proteins in all living cells. In yeast and in mammals, a system formed by an enzyme with ferroxidase activity coupled to a membrane transporter supports iron uptake or iron efflux, respectively. Ferroxidase belongs to the family of blue multicopper oxidases, enzymes able to couple the one-electron oxidation of substrate(s) to full reduction of molecular oxygen to water. On the other hand, the permeases are widely different and are specific to Fe3+ and Fe2+ in yeast and multicellular organisms, respectively. This review will describe the yeast and human ferroxidase–permease systems, highlighting similarities and differences in structure, function and regulation of the respective protein components.