Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila

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作   者：

Kosakamoto, Hina;  Okamoto, Naoki;  Aikawa, Hide;  Sugiura, Yuki;  Suematsu, Makoto;  Niwa, Ryusuke;  Miura, Masayuki;  Obata, Fumiaki; 

作者机构：

Keio Univ;  Univ Tsukuba;  Univ Tokyo; 

关键词：

GCN2;  DIETARY-PROTEIN;  METABOLISM;  GROWTH;  TRANSFER-RNA;  STRESS;  UP-REGULATION;  REDD1;  FGF21;  ATF4; 

期刊名称：

Nature Metabolism

i s s n：

年卷期：

2022 年 4 卷 7 期

页   码：

944-+

页   码：

摘   要：

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.