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

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)944-959
Number of pages16
JournalNature Metabolism
Issue number7
Publication statusPublished - 2022 Jul

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Cell Biology


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