ArticleThe EMBO journal2015
mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration.EMBO reports · 2026Article
- Review
- DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans.Nature communications · 2025Article
- Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation.Cancer research · 2025Article
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- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Morphodynamical adaptation of the endolysosomal system to stress.The FEBS journal · 2025Review
- The Rubicon-WIPI axis regulates exosome biogenesis during ageing.Nature cell biology · 2024Article
- A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.Autophagy · 2024Article
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- Recent progresses in the late stages of autophagy.Cell insight · 2024Review
- SNX8 enables lysosome reformation and reverses lysosomal storage disorder.Nature communications · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Oscillatory autophagy induction is enabled by an updated AMPK-ULK1 regulatory wiring.PloS one · 2024Article
- Genome-Wide Association Study Identifies the First Germline Genetic Variant Associated With Erdheim-Chester Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal ClBiomolecules · 2023Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrient-sensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome-lysosome reformation (ALR). Here we identify a lysosomal pool of phosphatidylinositol 3-phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3-kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process.
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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.