title: TORC1 inhibition induces lipid droplet replenishment in yeast.
abstract: Lipid droplets (LDs) are intracellular structures that regulate neutral lipid homeostasis. In mammals, LD synthesis is inhibited by rapamycin, a known inhibitor of the mTORC1 pathway. In Saccharomyces cerevisiae, LD dynamics are modulated by the growth phase; however, the regulatory pathways involved are unknown. Therefore, we decided to study the role of the TORC1 pathway on LD metabolism in S. cerevisiae. Interestingly, rapamycin treatment resulted in a fast LD replenishment and growth inhibition. The discovery that osmotic stress (1 M sorbitol) also induced LD synthesis but not growth inhibition suggested that the induction of LDs in yeast is not a secondary response to reduced growth. The induction of LDs by rapamycin was due to increased triacylglycerol but not sterol ester synthesis. Induction was dependent on the TOR downstream effectors, the PP2A-related phosphatase Sit4p and the regulatory protein Tap42p. The TORC1-controlled transcriptional activators Gln3p, Gat1p, Rtg1p, and Rtg3p, but not Msn2p and Msn4p, were required for full induction of LDs by rapamycin. Furthermore, we show that the deletion of Gln3p and Gat1p transcription factors, which are activated in response to nitrogen availability, led to abnormal LD dynamics. These results reveal that the TORC1 pathway is involved in neutral lipid homeostasis in yeast.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Juliana B
authors.initials: JB
authors.lastname: Madeira
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Masuda
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Maya-Monteiro
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gabriel Soares
authors.initials: GS
authors.lastname: Matos
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil montero@bioqmed.ufrj.br.
authors.forename: Mónica
authors.initials: M
authors.lastname: Montero-Lomelí
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Bozaquel-Morais
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D050980:GATA Transcription Factors / Q000172:deficiency / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D066292:Lipid Droplets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D009997:Osmotic Pressure; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002788:Cholesterol Esters; D050980:GATA Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054648:Protein Phosphatase 2; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D013012:Sorbitol; D014157:Transcription Factors; D014280:Triglycerides; C096100:GAT1 protein, S cerevisiae; C071664:GLN3 protein, S cerevisiae; C079378:RTG1 protein, S cerevisiae; C104438:RTG3 protein, S cerevisiae; C100984:TAP42 protein, S cerevisiae; C561842:TORC1 protein complex, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C104343:SIT4 protein, S cerevisiae