Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites

Sunil Laxman, Benjamin M. Sutter, Lei Shi, Benjamin P. Tu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Cells must be capable of switching between growth and autophagy in unpredictable nutrient environments. The conserved Npr2 protein complex (comprising Iml1, Npr2, and Npr3; also called SEACIT) inhibits target of rapamycin complex 1 (TORC1) kinase signaling, which inhibits autophagy in nutrient-rich conditions. In yeast cultured in media with nutrient limitations that promote autophagy and inhibit growth, loss of Npr2 enables cells to bypass autophagy and proliferate. We determined that Npr2-deficient yeast had a metabolic state distinct from that of wild-type yeast when grown in minimal media containing ammonium as a nitrogen source and a nonfermentable carbon source (lactate). Unlike wild-type yeast, which accumulated glutamine, Npr2-deficient yeast metabolized glutamine into nitrogen-containing metabolites and maintained a high concentration of S-adenosyl methionine (SAM). Moreover, in wild-type yeast grown in these nutrient-limited conditions, supplementation with methionine stimulated glutamine consumption for synthesis of nitrogenous metabolites, demonstrating integration of a sulfur-containing amino acid cue and nitrogen utilization. These data revealed the metabolic basis by which the Npr2 complex regulates cellular homeostasis and demonstrated a key function for TORC1 in regulating the synthesis and utilization of glutamine as a nitrogen source.

Original languageEnglish (US)
Article numberra120
JournalScience Signaling
Volume7
Issue number356
DOIs
StatePublished - Dec 16 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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