title: Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids.
abstract: Membrane phospholipids typically contain fatty acids (FAs) of 16 and 18 carbon atoms. This particular chain length is evolutionarily highly conserved and presumably provides maximum stability and dynamic properties to biological membranes in response to nutritional or environmental cues. Here, we show that the relative proportion of C16 versus C18 FAs is regulated by the activity of acetyl-CoA carboxylase (Acc1), the first and rate-limiting enzyme of FA de novo synthesis. Acc1 activity is attenuated by AMPK/Snf1-dependent phosphorylation, which is required to maintain an appropriate acyl-chain length distribution. Moreover, we find that the transcriptional repressor Opi1 preferentially binds to C16 over C18 phosphatidic acid (PA) species: thus, C16-chain containing PA sequesters Opi1 more effectively to the ER, enabling AMPK/Snf1 control of PA acyl-chain length to determine the degree of derepression of Opi1 target genes. These findings reveal an unexpected regulatory link between the major energy-sensing kinase, membrane lipid composition, and transcription.
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
authors: Harald F
authors: HF
authors: Hofbauer
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
authors: Florian H
authors: FH
authors: Schopf
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
authors: Hannes
authors: H
authors: Schleifer
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
authors: Oskar L
authors: OL
authors: Knittelfelder
authors: Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria.
authors: Bartholomäus
authors: B
authors: Pieber
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria; BioTechMed Graz, 8010 Graz, Austria.
authors: Gerald N
authors: GN
authors: Rechberger
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria; BioTechMed Graz, 8010 Graz, Austria.
authors: Heimo
authors: H
authors: Wolinski
authors: Department of Molecular Biology and Genetics, 249 Biotechnology Building, Cornell University, Ithaca, NY 14853-2703, USA.
authors: Maria L
authors: ML
authors: Gaspar
authors: Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria.
authors: C Oliver
authors: CO
authors: Kappe
authors: Protein Chemistry Facility, Institute of Molecular Pathology (IMP), Doktor-Bohr-Gasse 7, 1030 Vienna, Austria.
authors: Johannes
authors: J
authors: Stadlmann
authors: Protein Chemistry Facility, IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Doktor-Bohr-Gasse 3, 1030 Vienna, Austria.
authors: Karl
authors: K
authors: Mechtler
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
authors: Alexandra
authors: A
authors: Zenz
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria; BioTechMed Graz, 8010 Graz, Austria.
authors: Karl
authors: K
authors: Lohner
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria; BioTechMed Graz, 8010 Graz, Austria.
authors: Oksana
authors: O
authors: Tehlivets
authors: Department of Molecular Biology and Genetics, 249 Biotechnology Building, Cornell University, Ithaca, NY 14853-2703, USA.
authors: Susan A
authors: SA
authors: Henry
authors: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria; BioTechMed Graz, 8010 Graz, Austria. Electronic address: sepp.kohlwein@uni-graz.at.
authors: Sepp D
authors: SD
authors: Kohlwein
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008563:Membrane Lipids / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D007296:Myo-Inositol-1-Phosphate Synthase / Q000235:genetics* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / 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
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids; C096105:OPI1 protein, S cerevisiae; D010743:Phospholipids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C519641:INO1 protein, S cerevisiae; D007296:Myo-Inositol-1-Phosphate Synthase