Genome-wide screen for genes with effects on distinct iron uptake activities in Saccharomyces cerevisiae.
We screened a collection of 4847 haploid knockout strains (EUROSCARF collection) of Saccharomyces cerevisiae for iron uptake from the siderophore ferrioxamine B (FOB). A large number of mutants showed altered uptake activities, and a few turned yellow when grown on agar plates with added FOB, indicating increased intracellular accumulation of undissociated siderophores. A subset consisting of 197 knockouts with altered uptake was examined further for regulated activities that mediate cellular uptake of iron from other siderophores or from iron salts. Hierarchical clustering analysis grouped the data according to iron sources and according to mutant categories. In the first analysis, siderophores grouped together with the exception of enterobactin, which grouped with iron salts, suggesting a reductive pathway of iron uptake for this siderophore. Mutant groupings included three categories: (i) high-FOB uptake, high reductase, low-ferrous transport; (ii) isolated high- or low-FOB transport; and (iii) induction of all activities. Mutants with statistically altered uptake activities included genes encoding proteins with predominant localization in the secretory pathway, nucleus, and mitochondria. Measurements of different iron-uptake activities in the yeast knockout collection make possible distinctions between genes with general effects on iron metabolism and those with pathway-specific effects.
Laboratoire d'Ingéniérie des Protéines et Contrôle Métabolique, Département de Biologie des Génomes, Institut Jacques Monod, Unité Mixte de Recherche 7592 CNRS-Universités Paris 6 and 7, France. lesuisse@ijm.jussieu.fr
Emmanuel
E
Lesuisse
Simon A B
SA
Knight
Maïté
M
Courel
Renata
R
Santos
Jean-Michel
JM
Camadro
Andrew
A
Dancis
D001692:Biological Transport; D016000:Cluster Analysis; D003676:Deferoxamine / Q000378:metabolism* / Q000493:pharmacokinetics; D004758:Enterobactin / Q000378:metabolism / Q000493:pharmacokinetics; D038181:FMN Reductase / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D016681:Genome, Fungal; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D007502:Iron Chelating Agents / Q000378:metabolism / Q000493:pharmacokinetics; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism* / Q000493:pharmacokinetics
D005290:Ferric Compounds; D007502:Iron Chelating Agents; D029701:Saccharomyces cerevisiae Proteins; D017262:Siderophores; D004758:Enterobactin; C002577:ferrioxamine B; D007501:Iron; D038181:FMN Reductase; C023903:ferric citrate iron reductase; D003676:Deferoxamine