The intake of dietary protein regulates growth, metabolism, fecundity and lifespan across various species, which makes amino acid (AA)-sensing vital for adaptation to the nutritional environment. The general control nonderepressible 2 (GCN2)-activating transcription factor 4 (ATF4) pathway and the mechanistic target of rapamycin complex 1 (mTORC1) pathway are involved in AA-sensing. However, it is not fully understood which AAs regulate these two pathways in living animals and how they coordinate responses to protein restriction. Here we show in Drosophila that the non-essential AA tyrosine (Tyr) is a nutritional cue in the fat body necessary and sufficient for promoting adaptive responses to a low-protein diet, which entails reduction of protein synthesis and mTORC1 activity and increased food intake. This adaptation is regulated by dietary Tyr through GCN2-independent induction of ATF4 target genes in the fat body. This study identifies the Tyr–ATF4 axis as a regulator of the physiological response to a low-protein diet and sheds light on the essential function of a non-essential nutrient.

膳食蛋白质的摄入可调节各种物种的生长、新陈代谢、繁殖力和寿命，这使得氨基酸 (AA) 感应对于适应营养环境至关重要。一般控制非抑制性 2 (GCN2)-激活转录因子 4 (ATF4) 通路和雷帕霉素复合物 1 (mTORC1) 通路的机制靶点参与 AA 传感。然而，尚不完全了解哪些 AA 调节活体动物中的这两种途径，以及它们如何协调对蛋白质限制的反应。在这里，我们在果蝇中展示非必需的 AA 酪氨酸 (Tyr) 是脂肪体中的一种营养提示，对于促进对低蛋白饮食的适应性反应是必要和充分的，这需要减少蛋白质合成和 mTORC1 活性并增加食物摄入。这种适应受饮食 Tyr 调节，通过 GCN2 非依赖性诱导脂肪体中的 ATF4 靶基因。这项研究将 Tyr-ATF4 轴确定为对低蛋白饮食的生理反应的调节剂，并阐明了非必需营养素的基本功能。