FRE2

Fre2 is a ferric reductase encoded by the FRE2 gene in fungi, including Saccharomyces cerevisiae. It functions at the cell surface to reduce ferric iron (Fe3+) to ferrous iron (Fe2+), a step necessary for iron uptake in low-iron environments. The produced Fe2+ is then transported into the cell by the Fet3-Ftr1 iron uptake system, linking Fre2 to the high-affinity iron acquisition pathway.

Fre2 belongs to the ferric reductase family, which includes Fre1. In many yeasts, FRE1 and FRE2 have overlapping roles but are differentially expressed depending on iron status and growth conditions. Expression of FRE2 is regulated by iron availability and is controlled by iron-responsive transcription factors (Aft1/Aft2 in S. cerevisiae), with higher expression under iron limitation.

Protein topology is consistent with a membrane-associated reductase: the protein is anchored to the plasma membrane and oriented to transfer electrons from cytosolic donors to extracellular ferric chelates. The enzymatic activity requires electron donors such as NADPH, consistent with other ferric reductases.

Genetic studies show that loss of FRE2 impairs growth under iron-limited conditions and reduces iron uptake efficiency, though FRE1 can partly compensate. Beyond basic biology, FRE homologs are studied in pathogenic fungi, where iron acquisition via ferric reductases can influence virulence and adaptation to host environments. The term Fre2 commonly refers to the Saccharomyces cerevisiae FRE2 gene or its protein product, with homologs found across fungi.