title: TORC1 regulates Pah1 phosphatidate phosphatase activity via the Nem1/Spo7 protein phosphatase complex.
abstract: The evolutionarily conserved target of rapamycin complex 1 (TORC1) controls growth-related processes such as protein, nucleotide, and lipid metabolism in response to growth hormones, energy/ATP levels, and amino acids. Its deregulation is associated with cancer, type 2 diabetes, and obesity. Among other substrates, mammalian TORC1 directly phosphorylates and inhibits the phosphatidate phosphatase lipin-1, a central enzyme in lipid metabolism that provides diacylglycerol for the synthesis of membrane phospholipids and/or triacylglycerol as neutral lipid reserve. Here, we show that yeast TORC1 inhibits the function of the respective lipin, Pah1, to prevent the accumulation of triacylglycerol. Surprisingly, TORC1 regulates Pah1 in part indirectly by controlling the phosphorylation status of Nem1 within the Pah1-activating, heterodimeric Nem1-Spo7 protein phosphatase module. Our results delineate a hitherto unknown TORC1 effector branch that controls lipin function in yeast, which, given the recent discovery of Nem1-Spo7 orthologous proteins in humans, may be conserved.
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dubots
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cottier
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Péli-Gulli
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Malika
authors.initials: M
authors.lastname: Jaquenoud
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Séverine
authors.initials: S
authors.lastname: Bontron
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schneiter
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase