ArticlePLoS genetics2014
Beclin 1 is required for neuron viability and regulates endosome pathways via the UVRAG-VPS34 complex.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 131 citations in OpenAlex.
- Impact of BECLIN1 haploinsufficiency on goblet cell function and susceptibility to colitis.Cell death & disease · 2026Article
- Taliglucerase Alfa Reduces Amyloid-β Burden by Restoring Autophagic Pathways in a Neuronal Model of Alzheimer's Disease.Neurochemical research · 2026Article
- Mitochondria-derived vesicles with bioenergetic units from brown adipose tissue attenuate cardiac remodeling post-myocardial infarction.Nature communications · 2026Article
- Phosphatidylinositol-3-phosphate-dependent Klp98A recruitment regulates endosomal flux underlying developmental synaptic remodeling via Rab4.Journal of cell science · 2026Article
- Dexmedetomidine attenuates high-fat diet-induced metabolic dysfunction-associated steatotic liver disease in rats by regulating the autophagic pathway.Scientific reports · 2026Article
- Energy Deficiency-Induced ATG4B Nuclear Translocation Inhibits PRMT1-Mediated DNA Repair and Promotes Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025Review
- LRBA deficiency impairs autophagy and contributes to enhanced antigen presentation and T-cell dysregulation.EMBO reports · 2025Article
- Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function.Autophagy reports · 2025Article
- BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.Autophagy reports · 2025Review
- Article
- Repurposing Nano Curcumin: Unveiling its Therapeutic Potential in Diabetic Nephropathy.Current drug targets · 2025Review
- Endothelial HIFα/PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension.JCI insight · 2024Article
- Cisplatin Nephrotoxicity Is Critically Mediated by the Availability of BECLIN1.International journal of molecular sciences · 2024Article
- BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking.Communications biology · 2024Article
- Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Excessive Protein Accumulation and Impaired Autophagy in the Hippocampus of Angelman Syndrome Modeled in Mice.Biological psychiatry · 2023Article
- Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes.Autophagy · 2023Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases, but the molecular mechanism remains elusive. Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III (PI3K-III) lipid kinase activities regulate autophagy at different steps. Recent evidence suggests a function of beclin 1 in regulating multiple VPS34-mediated trafficking pathways beyond autophagy; however, the precise role of beclin 1 in autophagy-independent cellular functions remains poorly understood. Herein we report that beclin 1 regulates endocytosis, in addition to autophagy, and is required for neuron viability in vivo. We find that neuronal beclin 1 associates with endosomes and regulates EEA1/early endosome localization and late endosome formation. Beclin 1 maintains proper cellular phosphatidylinositol 3-phosphate (PI(3)P) distribution and total levels, and loss of beclin 1 causes a disruption of active Rab5 GTPase-associated endosome formation and impairment of endosome maturation, likely due to a failure of Rab5 to recruit VPS34. Furthermore, we find that Beclin 1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity. Interestingly, beclin 1 deficiency impairs p40phox-linked endosome formation, which is rescued by overexpressed UVRAG or beclin 1, but not by a coiled-coil domain-truncated beclin 1 (a UVRAG-binding mutant), Atg14L or RUBICON. Thus, our study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy, and suggests that the UVRAG-beclin 1 interaction underlies beclin 1's function in endocytosis.
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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.