ArticleNature cell biology2012
Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy.
Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.
- Nitrogen balance and outcomes in critically ill patients: A systematic review and meta-analysis.Frontiers in nutrition · 2022Pooled it
- A FoxO-Autophagy-Lipid Mobilization Axis Regulates Fat Body Remodeling During Honeybee Metamorphosis.Insects · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Dual activation of cuproptosis and excessive autophagy by copper-bismuth metal-organic frameworks-loaded detachable microneedles in oral leukoplakia.Materials today. Bio · 2026Article
- [Glutamine-induced autophagy exacerbates muscle atrophy in cachectic nude mice: a multi-omics analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer.EMBO reports · 2026Article
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Inhibition of glutamine synthetase enhances hepatocellular carcinoma radiosensitivity through ROS-induced excessive mitophagy.Molecular biology reports · 2025Article
- Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.Breast cancer research : BCR · 2025Article
- Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism.eLife · 2025Article
- Review
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- A novel and promising therapeutic approach for treating pancreatic cancer: Nectin‑4‑targeted antibody‑drug conjugates alone or combined with autophagy inhibitors.International journal of molecular medicine · 2025Article
- Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review.Frontiers in immunology · 2025Review
- GLUL stabilizes N-Cadherin by antagonizingActa pharmaceutica Sinica. B · 2024Article
- Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.Open medicine (Warsaw, Poland) · 2024Article
- Metabolic reprogramming in skin wound healing.Burns & trauma · 2024Review
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
87 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI(3)K-PKB-FOXO signalling network provides a major intracellular hub for the regulation of cell proliferation, survival and stress resistance. Here we report an unexpected role for FOXO transcription factors in regulating autophagy by modulating intracellular glutamine levels. To identify transcriptional targets of this network, we performed global transcriptional analyses after conditional activation of the key components PI(3)K, PKB/Akt, FOXO3 and FOXO4. Using this pathway approach, we identified glutamine synthetase as being transcriptionally regulated by PI(3)K-PKB-FOXO signalling. Conditional activation of FOXO also led to an increased level of glutamine production. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes in a glutamine-synthetase-dependent manner. This resulted in an increased level of autophagy as measured by LC3 lipidation, p62 degradation and fluorescent imaging of multiple autophagosomal markers. Inhibition of FOXO3-mediated autophagy increased the level of apoptosis, suggesting that the induction of autophagy by FOXO3-mediated glutamine synthetase expression is important for cellular survival. These findings reveal a growth-factor-responsive network that can directly modulate autophagy through the regulation of glutamine metabolism.
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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.