Defects in the yeast high affinity iron transport system result in increased metal sensitivity because of the increased expression of transporters with a broad transition metal specificity.
Yeast with defects in vacuolar pH show increased sensitivity to high concentrations of transition metals. This sensitivity has been presumed to result from defective metal storage. We demonstrate that mutations that result in a defective high affinity iron transport system, such as a deletion in the surface ferroxidase FET3, also result in increased metal sensitivity independent of vacuolar function. Multiple copies of transition metal transporter resistance genes, such as COT1 or ZRC1, do not reduce the metal sensitivity of fet3 mutations. Increased metal sensitivity is because of an increased cellular accumulation of transition metals resulting from the increased activity of low affinity iron transporters, such as FET4, that mediates the transport of other transition metals. In cells lacking a high affinity iron transport system, the increased transition metal uptake can be prevented by increased extracellular iron. These results suggest that vacuolar function may not be required for transition metal sequestration.
Division of Immunology and Cell Biology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
L
L
Li
J
J
Kaplan
D001483:Base Sequence; D001692:Biological Transport; D002570:Ceruloplasmin; D018118:Chloride Channels; D017931:DNA Primers; D005656:Fungal Proteins / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014617:Vacuoles / Q000378:metabolism
D018118:Chloride Channels; D017931:DNA Primers; D005656:Fungal Proteins; C089713:GEF1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron; D010088:Oxidoreductases; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae