title: Trehalose-6-phosphate synthesis controls yeast gluconeogenesis downstream and independent of SNF1.
abstract: Trehalose-6-P (T6P), an intermediate of trehalose biosynthesis, was identified as an important regulator of yeast sugar metabolism and signaling. tps1Δ mutants, deficient in T6P synthesis (TPS), are unable to grow on rapidly fermentable medium with uncontrolled influx in glycolysis, depletion of ATP and accumulation of sugar phosphates. However, the exact molecular mechanisms involved are not fully understood. We show that SNF1 deletion restores the tps1Δ growth defect on glucose, suggesting that lack of TPS hampers inactivation of SNF1 or SNF1-regulated processes. In addition to alternative, non-fermentable carbon metabolism, SNF1 controls two major processes: respiration and gluconeogenesis. The tps1Δ defect appears to be specifically associated with deficient inhibition of gluconeogenesis, indicating more downstream effects. Consistently, Snf1 dephosphorylation and inactivation on glucose medium are not affected, as confirmed with an in vivo Snf1 activity reporter. Detailed analysis shows that gluconeogenic Pck1 and Fbp1 expression, protein levels and activity are not repressed upon glucose addition to tps1Δ cells, suggesting a link between the metabolic defect and persistent gluconeogenesis. While SNF1 is essential for induction of gluconeogenesis, T6P/TPS is required for inactivation of gluconeogenesis in the presence of glucose, downstream and independent of SNF1 activity and the Cat8 and Sip4 transcription factors.
authors.affiliation: Laboratory of Molecular Plant Biology, Department of Biology, KU Leuven, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Deroover
authors.affiliation: Laboratory of Functional Biology, Department of Biology, KU Leuven, B-3001 Leuven, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Ghillebert
authors.affiliation: Laboratory of Molecular Plant Biology, Department of Biology, KU Leuven, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Broeckx
authors.affiliation: Laboratory of Functional Biology, Department of Biology, KU Leuven, B-3001 Leuven, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
authors.affiliation: Laboratory of Molecular Plant Biology, Department of Biology, KU Leuven, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium filip.rolland@bio.kuleuven.be.
authors.forename: Filip
authors.initials: F
authors.lastname: Rolland
mesh_terms: D003470:Culture Media / Q000737:chemistry; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013403:Sugar Phosphates / Q000378:metabolism*; D014199:Trehalose / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D003470:Culture Media; D013403:Sugar Phosphates; C082722:trehalose-6-phosphate; D014199:Trehalose; D005964:Glucosyltransferases; C023180:trehalose-6-phosphate synthase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose
keywords: SNF1; TPS; gluconeogenesis; trehalose-6-P