ArticleThe Journal of biological chemistry2022
Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Dual Roles of Autophagy in Endometrial Fibrosis and Its Implications in Age-Related Reproductive Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Physiological temperature enhances proliferative capacity and protein production characteristics of chick satellite cells.Food science of animal resources · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Dietary Supplementation with Hesperidin and Rosmarinic Acid Improves Meat Quality, Modulates Gut Microbiota, and Enhances Antioxidant Capacity in Finishing Pigs.Microorganisms · 2026Article
- RNA helicase SKIV2L impedes tumor immunity by reprogramming arginine metabolism of hepatocellular carcinomas.Journal for immunotherapy of cancer · 2026Article
- Article
- Antidepressant Effects of L-Arginine and Its Role in Brain Energy MetabolismIranian biomedical journal · 2026Article
- Peripheral lysosome levels dictate mTORC1 inactivation even when catabolically impaired.Cell communication and signaling : CCS · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Exercise-Induced Molecular Adaptations in Chronic Non-Communicable Diseases-Narrative Review.International journal of molecular sciences · 2025Review
- Metabolic-transcriptional rewiring by NFE2L2 promotes M2 macrophage polarization and anti-PD-L1 resistance in glioma.Cancer cell international · 2025Article
- Analysis of the Stimulative Effect of Arginine on Translation Initiation of Protein Synthesis in Skeletal Muscle.Nutrients · 2025Article
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
- Crosstalk between dysregulated amino acid sensing and glucose and lipid metabolism in colorectal cancer.Frontiers in oncology · 2025Review
- Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.Frontiers in endocrinology · 2025Review
- Transmembrane Amino Acid Transporters in Shaping the Metabolic Profile of Breast Cancer Cell Lines: The Focus on Molecular Biological Subtype.Current issues in molecular biology · 2024Review
- Starvation-induced metabolic rewiring affects mTORC1 composition in vivo.Scientific reports · 2024Article
- Arf1 promotes porcine intestinal epithelial cell proliferation via the mTORC1 signaling pathway.In vitro cellular & developmental biology. Animal · 2024Article
- Analgesic Effect of Human Placenta Hydrolysate on CFA-Induced Inflammatory Pain in Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Balancing lysosome abundance in health and disease.Nature cell biology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase complex that promotes anabolic processes including protein, lipid, and nucleotide synthesis, while suppressing catabolic processes such as macroautophagy. mTORC1 activity is regulated by growth factors and amino acids, which signal through distinct but integrated molecular pathways: growth factors largely signal through the PI3K/Akt-dependent pathway, whereas the availabilities of amino acids leucine and arginine are communicated to mTORC1 by the Rag-GTPase pathway. While it is relatively well described how acute changes in leucine and arginine levels affect mTORC1 signaling, the effects of prolonged amino acid deprivation remain less well understood. Here, we demonstrate that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, which reaches activation levels similar to those observed in nutrient-rich conditions. Surprisingly, we find that this reactivation is independent of the regeneration of amino acids by canonical autophagy or proteasomal degradation but is dependent on PI3K/Akt signaling. Together, our data identify a novel crosstalk between the amino acid and PI3K/Akt signaling pathways upstream of mTORC1. These observations extend our understanding of the role of mTORC1 in growth-related diseases and indicate that dietary intervention by removal of leucine and/or arginine may be an ineffective therapeutic approach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.