ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- 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
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Amino acid metabolic signatures of dynapenic obesity in older adults: a (principal component analysis) PCA-based sex-stratified analysis in the Bushehr elderly health program.Journal of diabetes and metabolic disorders · 2025Article
- Methionine deficiency causes spermatogonial apoptosis via oxidative stress and DNA damage response pathway.Biological research · 2025Article
- Article
- Autophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.The Journal of biological chemistry · 2025Article
- High-level L-Gln compromises intestinal amino acid utilization efficiency and inhibits protein synthesis by GCN2/eIF2α/ATF4 signaling pathway in piglets fed low-crude protein diets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.American journal of physiology. Endocrinology and metabolism · 2024Article
- Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction.GeroScience · 2023Article
- Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction.Frontiers in aging · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dietary removal of an essential amino acid (EAA) triggers the integrated stress response (ISR) in liver. Herein, we explored the mechanisms that activate the ISR and execute changes in transcription and translation according to the missing EAA. Wild-type mice and mice lacking general control nonderepressible 2 (Gcn2) were fed an amino acid complete diet or a diet devoid of either leucine or sulfur amino acids (methionine and cysteine). Serum and liver leucine concentrations were significantly reduced within the first 6 h of feeding a diet lacking leucine, corresponding with modest, GCN2-dependent increases in Atf4 mRNA translation and induction of selected ISR target genes (Fgf21, Slc7a5, Slc7a11). In contrast, dietary removal of the sulfur amino acids lowered serum methionine, but not intracellular methionine, and yet hepatic mRNA abundance of Atf4, Fgf21, Slc7a5, Slc7a11 substantially increased regardless of GCN2 status. Liver tRNA charging levels did not correlate with intracellular EAA concentrations or GCN2 status and remained similar to mice fed a complete diet. Furthermore, loss of Gcn2 increased the occurrence of ribosome collisions in liver and derepressed mechanistic target of rapamycin complex 1 signal transduction, but these changes did not influence execution of the ISR. We conclude that ISR activation is directed by intracellular EAA concentrations, but ISR execution is not. Furthermore, a diet devoid of sulfur amino acids does not require GCN2 for the ISR to execute changes to the transcriptome.
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