@article{3e6a8d122bec4f00bf1815d76053eb6f,
title = "Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila",
abstract = "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.",
author = "Hina Kosakamoto and Naoki Okamoto and Hide Aikawa and Yuki Sugiura and Makoto Suematsu and Ryusuke Niwa and Masayuki Miura and Fumiaki Obata",
note = "Funding Information: We acknowledge A. P. Gould (the Francis Crick Institute), H. D. Ryoo (New York University School of Medicine), W.J. Lee (Seoul National University), R. Carthew (Northwestern University), O. V. Alekseyenko (Harvard Medical School), the Kyoto Stock Center, National Institute of Genetics, Vienna Drosophila Resource Center and Bloomington Drosophila Stock Center for reagents. We thank S. Sorge, A. Franchet, L. Lampe, A. P. Gould and Y. Yoshinari for critical comments on the manuscript. We thank T. Fujisawa, T. Ichinose, H. Tanimoto and all members of our laboratory for technical assistance and critical advice. We appreciate the generous support of Shimadzu, which provided the LC–MS platform for the Suematsu laboratory but did not participate in designing the study or analyzing the data. This work was supported by AMED-PRIME to F.O. under grant nos. JP17gm6010010 and JP20gm6310011 and by AMED-Project for Elucidating and Controlling Mechanisms of Aging and Longevity to M.M under grant no. JP21gm5010001. This work was also supported by grants from the Japan Society for the Promotion of Science to F.O. under grant nos. 19H03367, 20H05726 and 22H02769 and to M.M. under grant nos. 16H06385, 21H04774 and 21K19206. This work was partially supported by the Uehara Memorial Foundation to F.O., the Tomizawa Jun-ichi & Keiko Fund of the Molecular Biology Society of Japan for Young Scientists to N.O. and F.O. and the Cooperative Research Project Program of Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA Center), University of Tsukuba, Japan. H.K. is a JSPS research fellow. Funding Information: We acknowledge A. P. Gould (the Francis Crick Institute), H. D. Ryoo (New York University School of Medicine), W.J. Lee (Seoul National University), R. Carthew (Northwestern University), O. V. Alekseyenko (Harvard Medical School), the Kyoto Stock Center, National Institute of Genetics, Vienna Drosophila Resource Center and Bloomington Drosophila Stock Center for reagents. We thank S. Sorge, A. Franchet, L. Lampe, A. P. Gould and Y. Yoshinari for critical comments on the manuscript. We thank T. Fujisawa, T. Ichinose, H. Tanimoto and all members of our laboratory for technical assistance and critical advice. We appreciate the generous support of Shimadzu, which provided the LC–MS platform for the Suematsu laboratory but did not participate in designing the study or analyzing the data. This work was supported by AMED-PRIME to F.O. under grant nos. JP17gm6010010 and JP20gm6310011 and by AMED-Project for Elucidating and Controlling Mechanisms of Aging and Longevity to M.M under grant no. JP21gm5010001. This work was also supported by grants from the Japan Society for the Promotion of Science to F.O. under grant nos. 19H03367, 20H05726 and 22H02769 and to M.M. under grant nos. 16H06385, 21H04774 and 21K19206. This work was partially supported by the Uehara Memorial Foundation to F.O., the Tomizawa Jun-ichi & Keiko Fund of the Molecular Biology Society of Japan for Young Scientists to N.O. and F.O. and the Cooperative Research Project Program of Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA Center), University of Tsukuba, Japan. H.K. is a JSPS research fellow. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = jul,
doi = "10.1038/s42255-022-00608-7",
language = "English",
volume = "4",
pages = "944--959",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Berlin",
number = "7",
}
