Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila
Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila
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DOI：
10.1038/s42255-022-00608-7
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发表时间：
2022-07-01
影响因子：
20.8
通讯作者：
Obata, Fumiaki
中科院分区：
文献类型：
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作者：
Kosakamoto, Hina;Okamoto, Naoki;Obata, Fumiaki
氨基酸感应对于适应营养环境至关重要。在这项研究中，小坂本等人。研究表明，非必需氨基酸酪氨酸通过调节果蝇 ATF4 活性来调节对蛋白质限制的适应性反应。膳食蛋白质的摄入可调节不同物种的生长、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。一般控制非阻抑物 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，目前尚不完全了解哪些氨基酸在活体动物中调节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，我们在果蝇中证明，非必需 AA 酪氨酸 (Tyr) 是脂肪体内的一种营养提示，对于促进对低蛋白饮食的适应性反应是必要且充分的，这需要减少蛋白质合成和 mTORC1 活性并增加食物摄入量。这种适应是通过饮食中的 Tyr 通过 GCN2 独立诱导脂肪体内的 ATF4 靶基因来调节的。这项研究确定了 Tyr-ATF4 轴作为低蛋白饮食生理反应的调节因子，并揭示了非必需营养素的基本功能。
Amino acid-sensing is vital for adaptation to the nutritional environment. In this study, Kosakamoto et al. show that the non-essential amino acid tyrosine regulates the adaptive response to protein restriction via modulating ATF4 activity in Drosophila.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.