THE AFT1 TRANSCRIPTIONAL FACTOR IS DIFFERENTIALLY REQUIRED FOR EXPRESSION OF HIGH-AFFINITY IRON UPTAKE GENES IN SACCHAROMYCES-CEREVISIAE

High-affinity iron uptake in Saccharomyces cerevisiae involves the ext racytoplasmic reduction of ferric ions by FRE1 and FRE2 reductases. Fe rrous ions are then transported across the plasma membrane through the FET3 oxidase-FTR1 permease complex. Expression oi the high-affinity i ron uptake genes is induced upon iron deprivation. We demonstrate that AFT1 is differentially involved in such regulation. Aft1 protein is r equired for maintaining detectable non-induced levels of FET3 expressi on and for induction of FRE1 in iron starvation conditions. On the con trary, 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 wa y. The alterations in the basal levels of expression of the high-affin ity iron uptake genes may explain why the AFT1 mutant is unable to gro w on respirable carbon sources. Overexpression of AFT1 leads to growth arrest at the G(1) stage of the cell cycle. Aft1 is a transcriptional activator that would be part of the different transcriptional complex es interacting with the promoter of the high-affinity iron uptake gene s. Aft1 displays phosphorylation modifications depending on the growth stage of the cells, and it might link induction of genes for iron upt ake to other metabolically dominant requirements for cell growth. (C) 1997 by John Wiley & Sons, Ltd.