title: Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism.
abstract: Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate headgroup. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: Barry P
authors.initials: BP
authors.lastname: Young
authors.forename: John J H
authors.initials: JJ
authors.lastname: Shin
authors.forename: Rick
authors.initials: R
authors.lastname: Orij
authors.forename: Jesse T
authors.initials: JT
authors.lastname: Chao
authors.forename: Shu Chen
authors.initials: SC
authors.lastname: Li
authors.forename: Xue Li
authors.initials: XL
authors.lastname: Guan
authors.forename: Anthony
authors.initials: A
authors.lastname: Khong
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: William A
authors.initials: WA
authors.lastname: Prinz
authors.forename: Gertien J
authors.initials: GJ
authors.lastname: Smits
authors.forename: Christopher J R
authors.initials: CJ
authors.lastname: Loewen
mesh_terms: D021581:Active Transport, Cell Nucleus; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007294:Inositol / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D009154:Mutation; D010712:Phosphatidic Acids / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D008081:Liposomes; C096105:OPI1 protein, S cerevisiae; D010712:Phosphatidic Acids; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C068664:TRK1 protein, S cerevisiae; D007294:Inositol; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; C092477:PMA1 protein, S cerevisiae; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; D005947:Glucose