title: The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae.
abstract: Saccharomyces cerevisiae takes up siderophore-bound iron through two distinct systems, one that requires siderophore transporters of the ARN family and one that requires the high affinity ferrous iron transporter on the plasma membrane. Uptake through the plasma membrane ferrous iron transporter requires that the iron first must dissociate from the siderophore and undergo reduction to the ferrous form. FRE1 and FRE2 encode cell surface metalloreductases that are required for reduction and uptake of free ferric iron. The yeast genome contains five additional FRE1 and FRE2 homologues, four of which are regulated by iron and the major iron-dependent transcription factor, Aft1p, but whose function remains unknown. Fre3p was required for the reduction and uptake of ferrioxamine B-iron and for growth on ferrioxamine B, ferrichrome, triacetylfusarinine C, and rhodotorulic acid in the absence of Fre1p and Fre2p. By indirect immunofluorescence, Fre3p was expressed on the plasma membrane in a pattern similar to that of Fet3p, a component of the high affinity ferrous transporter. Enterobactin, a catecholate siderophore, was not a substrate for Fre3p, and reductive uptake required either Fre1p or Fre2p. Fre4p could facilitate utilization of rhodotorulic acid-iron when the siderophore was present in higher concentrations. We propose that Fre3p and Fre4p are siderophore-iron reductases and that the apparent redundancy of the FRE genes confers the capacity to utilize iron from a variety of siderophore sources.
authors: Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1800, USA.
authors: C W
authors: CW
authors: Yun
authors: M
authors: M
authors: Bauler
authors: R E
authors: RE
authors: Moore
authors: P E
authors: PE
authors: Klebba
authors: C C
authors: CC
authors: Philpott
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D003676:Deferoxamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004758:Enterobactin / Q000378:metabolism / Q000493:pharmacokinetics; D038181:FMN Reductase; D005290:Ferric Compounds / Q000378:metabolism; D005291:Ferrichrome / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000493:pharmacokinetics*; D026901:Membrane Transport Proteins; D008856:Microscopy, Fluorescence; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D010088:Oxidoreductases / Q000378:metabolism / Q000502:physiology*; D010879:Piperazines / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D017262:Siderophores / Q000378:metabolism / Q000493:pharmacokinetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C090297:AFT1 protein, S cerevisiae; C409889:ARN2 protein, S cerevisiae; D002352:Carrier Proteins; D005290:Ferric Compounds; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D010879:Piperazines; D029701:Saccharomyces cerevisiae Proteins; D017262:Siderophores; D014157:Transcription Factors; D005291:Ferrichrome; D004758:Enterobactin; C002577:ferrioxamine B; C003305:rhodotorulic acid; D007501:Iron; D010088:Oxidoreductases; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase; D003676:Deferoxamine