ArticleAutophagy2023
Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Extracellular Mitochondria Mediate Endothelial Injury After Traumatic Brain Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- ANKRD1 expression and functional mechanism in stomach adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- O-GlcNAcylation Regulation of SNAP29-Dependent Autophagy Activation Dictates Chemoresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- PYGL-driven glycogenolysis impairs microglial autophagic fluxActa pharmaceutica Sinica. B · 2026Article
- Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).International journal of molecular medicine · 2026Review
- An ROS-responsive, RGC-targeted nanotherapeutic strategy with a TRPV4 antagonist restores autophagic flux and protects RGCs in a rat model of chronic ocular hypertension.Journal of nanobiotechnology · 2026Article
- α-tubulin N-acetyltransferase 1 regulates NCOA4-mediated ferritinophagy and protects cancer cells from ferroptosis.Cellular & molecular biology letters · 2026Article
- The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.Journal of extracellular vesicles · 2026Article
- Indole-3-Propionic Acid Improves Alveolar Development Impairment via Targeting VAMP8-mediated SNAREs Complex Formation in Bronchopulmonary Dysplasia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Cells to Animals: Connexin43 Suppression Enhances Autophagic Flux to Restore Odontogenesis in Inflamed Dental Pulp.International endodontic journal · 2026Article
- Targeting UAP1 with rabeprazole: a novel repurposed therapeutic strategy for multiple myeloma.Frontiers in pharmacology · 2026Article
- Regulatory mechanism of O-linked N-acetylglucosamine protein modification on autophagy in cancer.Clinical and translational medicine · 2026Review
- A small-molecule anti-cancer drug for long-acting lysosomal damage.Acta pharmaceutica Sinica. B · 2025Article
- O‑GlcNAcylation: The crosstalk between infection immunity and autophagy in sepsis (Review).Molecular medicine reports · 2025Review
- O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review).Oncology reports · 2025Review
- Identification of Proteomic Biomarkers and Therapeutic Targets for Vitiligo Using a Two-Sample Proteome-Wide Mendelian Randomization Approach.Journal of cosmetic dermatology · 2025Article
- Review
- Polystyrene nanoplastics trigger pyroptosis in dopaminergic neurons through TSC2/TFEB-mediated disruption of autophagosome-lysosome fusion in Parkinson's disease.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases.
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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.