Fet3Ftr1

Fet3Ftr1 refers to the heteromeric iron uptake complex formed by Fet3, a multicopper oxidase, and Ftr1, a membrane iron permease, found in several fungal species. This complex mediates high-affinity uptake of ferric iron from the extracellular environment, a critical process when iron is scarce. Fet3 oxidizes Fe2+ to Fe3+, and the resulting ferric iron is transported into the cell through Ftr1, enabling efficient iron acquisition under limiting conditions.

Structure and function are defined by the partnership between Fet3 and Ftr1 at the plasma membrane. Fet3 requires copper as a cofactor for its oxidase activity, and maturation of Fet3 depends on functional copper delivery systems. Ftr1 provides the membrane conduit for ferric iron transfer. The interaction between Fet3 and Ftr1 is essential for activity, and disruption of either component impairs high-affinity iron uptake.

Regulation of Fet3Ftr1 expression is tightly linked to iron availability. In the model yeast Saccharomyces cerevisiae, iron deficiency upregulates FET3 and FTR1 transcription through iron-responsive regulatory networks involving transcription factors such as Aft1 and Aft2. Copper status can also influence Fet3 maturation and activity, linking copper and iron homeostasis in the pathway.

Biological significance and applications: The Fet3Ftr1 system is a widely studied model of eukaryotic high-affinity iron uptake and has implications for the virulence of several pathogenic fungi, where iron acquisition supports growth in host environments. Because the complex is not present in mammals, it has been explored as a potential target for antifungal strategies. Ongoing research aims to clarify stoichiometry, regulatory circuits, and the detailed mechanism of iron translocation through Ftr1.