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.

由Iml1-Npr2-Npr3组成的GATOR1（SEACIT）复合物可抑制氨基酸不足，从而抑制雷帕霉素复合物1（TORC1）的靶标。在葡萄糖培养基中，尽管显示出TORC1信号转导增加的特征，但缺乏这种复合物功能的酿酒酵母突变体在缺乏氨基酸补充的情况下生长较差。此类突变体感觉到它们富含氨基酸，因此抑制了对于实现该状态至关重要的代谢活性。我们发现npr2Δ突变体具有缺陷的线粒体三羧酸（TCA）循环活性和逆行反应。补充谷氨酰胺，尤其是天冬氨酸，这是三氮杂磷循环中间体的含氮形式，可拯救npr2Δ的生长突变体。这些氨基酸随后在需要氮以支持增生代谢的生物合成途径中被消耗。我们的发现表明，TORC1的负调控因子，例如GATOR1（SEACIT），可以调节TCA循环中这些氨基酸的分解酶合成，并与细胞的氨基酸和氮素状态保持一致。