title: Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance.
abstract: Control of lipid composition of membranes is crucial to ensure normal cellular functions. Saccharomyces cerevisiae has two different phosphatidylserine decarboxylase enzymes (Psd1 and Psd2) that catalyze formation of phosphatidylethanolamine. The mitochondrial Psd1 provides roughly 70% of the phosphatidylethanolamine (PE) biosynthesis in the cell with Psd2 carrying out the remainder. Here, we demonstrate that loss of Psd2 causes cells to acquire sensitivity to cadmium even though Psd1 remains intact. This cadmium sensitivity results from loss of normal activity of a vacuolar ATP-binding cassette transporter protein called Ycf1. Measurement of phospholipid levels indicates that loss of Psd2 causes a specific reduction in vacuolar membrane PE levels, whereas total PE levels are not significantly affected. The presence of a phosphatidylinositol transfer protein called Pdr17 is required for Psd2 function and normal cadmium tolerance. We demonstrate that Pdr17 and Psd2 form a complex in vivo that seems essential for maintenance of vacuolar PE levels. Finally, we refine the localization of Psd2 to the endosome arguing that this enzyme controls vacuolar membrane phospholipid content by regulating phospholipids in compartments that will eventually give rise to the vacuole. Disturbance of this regulation of intracellular phospholipid balance leads to selective loss of membrane protein function in the vacuole.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kailash
authors.initials: K
authors.lastname: Gulshan
authors.forename: Puja
authors.initials: P
authors.lastname: Shahi
authors.forename: W Scott
authors.initials: WS
authors.lastname: Moye-Rowley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000096:biosynthesis*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018528:ATP-Binding Cassette Transporters; D007527:Isoenzymes; D008563:Membrane Lipids; C492205:PDR17 protein, S cerevisiae; D010714:Phosphatidylethanolamines; D049294:Phospholipid Transfer Proteins; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; C083241:SNC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; D002104:Cadmium; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase