Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism

Science. 2010 Aug 27;329(5995):1085-8. doi: 10.1126/science.1191026.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cell Membrane / metabolism*
  • Cell Nucleus / metabolism
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Glucose / metabolism
  • Hydrogen-Ion Concentration
  • Inositol / genetics
  • Inositol / metabolism
  • Liposomes / metabolism
  • Mutation
  • Phosphatidic Acids / metabolism*
  • Protein Binding
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Transcription, Genetic
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Cation Transport Proteins
  • Liposomes
  • OPI1 protein, S cerevisiae
  • Phosphatidic Acids
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • TRK1 protein, S cerevisiae
  • Inositol
  • Protein Phosphatase 1
  • REG1 protein, S cerevisiae
  • PMA1 protein, S cerevisiae
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases
  • Glucose