GATOR1 regulates nitrogenic cataplerotic reactions of the mitochondrial TCA cycle

Nat Chem Biol. 2017 Nov;13(11):1179-1186. doi: 10.1038/nchembio.2478. Epub 2017 Sep 18.


The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks of increased TORC1 signaling. Such mutants sense that they are amino acid replete and thus repress metabolic activities that are important for achieving this state. We found that npr2Δ mutants have defective mitochondrial tricarboxylic acid (TCA)-cycle activity and retrograde response. Supplementation with glutamine, and especially aspartate, which are nitrogen-containing forms of TCA-cycle intermediates, rescues growth of npr2Δ mutants. These amino acids are then consumed in biosynthetic pathways that require nitrogen to support proliferative metabolism. Our findings revealed that negative regulators of TORC1, such as GATOR1 (SEACIT), regulate the cataplerotic synthesis of these amino acids from the TCA cycle, in tune with the amino acid and nitrogen status of cells.

MeSH terms

  • Aspartic Acid / metabolism
  • Citric Acid Cycle*
  • Glutamine / metabolism
  • Mitochondria / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Nitrogen / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Multiprotein Complexes
  • Mutant Proteins
  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors
  • Glutamine
  • Aspartic Acid
  • Nitrogen