High-affinity iron uptake in Saccharomyces cerevisiae involves the 
extracytoplasmic reduction of ferric ions by FRE1 and FRE2 reductases. Ferrous 
ions are then transported across the plasma membrane through the FET3 
oxidase-FTR1 permease complex. Expression of the high-affinity iron uptake genes 
is induced upon iron deprivation. We demonstrate that AFT1 is differentially 
involved in such regulation. Aft1 protein is required for maintaining detectable 
non-induced level of FET3 expression and for induction of FRE2 in iron 
starvation conditions. On the contrary, FRE1 mRNA induction is normal in the 
absence of Aft1, although the existence of AFT1 point mutations causing 
constitutive expression of FRE1 (Yamaguchi-Iwai et al., EMBO J. 14: 1231-1239, 
1995) indicates that Aft1 may also participate in FRE1 expression in a 
dispensable way. The alterations in the basal levels of expression of the 
high-affinity iron uptake genes may explain why the AFT1 mutant is unable to 
grow on respirable carbon sources. Overexpression of AFT1 leads to growth arrest 
of the G1 stage of the cell cycle. Aft1 is a transcriptional activator that 
would be part of the different transcriptional complexes interacting with the 
promoter of the high-affinity iron uptake genes. Aft1 displays phosphorylation 
modifications depending on the growth stage of the cells, and it might link 
induction of genes for iron uptake to other metabolically dominant requirement 
for cell growth.