ArticleNature metabolism2022
Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
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- Optimal standardized ileal digestible lysine levels in low-protein diets: Effects on performance of lactating sows and their offspring.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Dietary restriction is evolutionarily conserved on the phenotypic and mechanistic level.EMBO reports · 2026Article
- Cytoplasmic fluidity couples nutrient availability and enterocyte fate in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sexually dimorphic ATF4 expression in the fat confers female stress tolerance in Drosophila melanogaster.Genetics · 2026Article
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Remote regulation of hepatic lipid secretion in the intestine by metabolic interaction of dietary arginine with ornithine.Scientific reports · 2026Article
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- 4EHP and NELF-E regulate physiological ATF4 induction and proteostasis in disease models of Drosophila.Nature communications · 2025Article
- Temporal changes in amino acid profiles coordinate mosquito physiology and egg maturation in Aedes aegypti.BMC biology · 2025Article
- The blood-brain barrier regulates brain tumor growth through the SLC36 amino acid transporter Pathetic in Drosophila.PLoS biology · 2025Article
- The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study.Aging · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan.Nature metabolism · 2025Article
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- Selection for Early Reproduction Leads to Accelerated Aging and Extensive Metabolic Remodeling in Drosophila melanogaster.Genome biology and evolution · 2025Article
- Comparative Transcriptome Analysis Reveals the Effects of a High-Protein Diet on Silkworm Midgut.Insects · 2025Article
- Gap junctions allow transfer of metabolites between germ cells and somatic cells to promote germ cell growth in the Drosophila ovary.PLoS biology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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