Summary: MOLECULAR AND CELLULAR BIOLOGY, May 1994, p. 3065-3073 Vol. 14, No. 5
Copyright C) 1994, American Society for Microbiology
Two Distinctly Regulated Genes Are Required for Ferric
Reduction, the First Step of Iron Uptake in
ELENA GEORGATSOU' AND DESPINA ALEXANDRAKI12*
Foundation for Research and Technology-HELLAS, Institute ofMolecular Biology and Biotechnology,'
and Department ofBiology, University of Crete,2 Heraklion 711 10, Crete, Greece
Received 1 October 1993/Returned for modification 29 November 1993/Accepted 3 February 1994
Iron uptake in Saccharomyces cerevisiae involves at least two steps: reduction of ferric to ferrous ions
extracellularly and transport of the reduced ions through the plasma membrane. We have cloned and
molecularly characterized FRE2, a gene which is shown to account, together with FREI, for the total
membrane-associated ferric reductase activity of the cell. Although not similar at the nucleotide level, the two
genes encode proteins with significantly similar primary structures and very similar hydrophobicity profiles.
The FRE1 and FRE2 proteins are functionally related, having comparable properties as ferric reductases.
FRE2 expression, like FREI expression, is induced by iron deprivation, and at least part of this control takes
place at the transcriptional level, since 156 nucleotides upstream of the initiator AUG conferred iron-
dependent regulation when fused to a heterologous gene. However, the two gene products have distinct
temporal regulation of their activities during cell growth.