Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid.
Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast Saccharomyces cerevisiae can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.
Loewen
C J R
CJ
Division of Cell Biology, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Gaspar
M L
ML
Jesch
S A
SA
Delon
C
C
Ktistakis
N T
NT
Henry
S A
SA
Levine
T P
TP
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D003567:Cytidine Diphosphate Diglycerides; D008081:Liposomes; C096105:OPI1 protein, S cerevisiae; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D007294:Inositol