ArticleLife metabolism2023
Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK.
Article in Life metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
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- Rab4b controls hepatic glucose production during fasting through glycophagy.Nature communications · 2026Article
- Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance.Cancer pathogenesis and therapy · 2026Review
- Integrated Transcriptomic and Metabolomic Analysis Reveals the Meat Production Features in Hybrid Sheep.Animals : an open access journal from MDPI · 2026Article
- Lysosomal dysfunction in diabetes and diabetic complications.Frontiers in endocrinology · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.Cell research · 2025Article
- Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease.Metabolism open · 2025Article
- A lysosomal surveillance response promotes healthspan inMetabolism open · 2025Article
- Oligodendrocyte precursor cell-specific blocking of low-glucose-induced activation of AMPK ensures myelination and remyelination.Nature metabolism · 2025Article
- Article
- Energy Metabolism and Brain Aging: Strategies to Delay Neuronal Degeneration.Cellular and molecular neurobiology · 2025Review
- D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint.Journal of hematology & oncology · 2025Article
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.Cell research · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When glucose is replete, mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is active and anchored to the lysosomal surface via the two GTPases, Ras-related GTPase (RAG) and Ras homolog enriched in brain (Rheb), which are regulated by Ragulator and tuberous sclerosis complex 2 (TSC2), respectively. When glucose is low, aldolase senses low fructose-1,6-bisphosphate level and promotes the translocation of AXIN-liver kinase B1 (LKB1) to the lysosomal surface, which leads to the activation of AMP-activated protein kinase (AMPK) and the inhibition of RAGs, sundering mTORC1 from the lysosome and causing its inactivation. AMPK can also inactivate mTORC1 by phosphorylating Raptor and TSC2. However, the hierarchy of AXIN- and AMPK-mediated inhibition of mTORC1 remains poorly defined. Here, we show that AXIN translocation does not require AMPK expression or activity. In glucose starvation conditions, knockout of AXIN extended the half-life of mTORC1 inhibition from 15 to 60 min, whereas knockout of AMPK only extended it to 30 min. RAGB
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