ArticleThe Journal of biological chemistry2017
Accumulation of autophagosomes confers cytotoxicity.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- The interplay between oxidative stress and autophagy in chronic obstructive pulmonary disease.Frontiers in physiology · 2022Pooled it
- 1,2-Dichloroethane Induces Neuronal Apoptosis Through AMPK-mTOR-ULK1 Pathway Activation and Autophagic Flux Impairment.Biology · 2026Article
- BUB1 regulates cell proliferation and apoptosis in cervical cancer by AKT signaling and autophagosome-lysosome fusion via ACTN1.iScience · 2026Article
- Simultaneous activation and late-stage inhibition of autophagy induces autophagy-dependent cell death in leukemia.BMC cancer · 2026Article
- Secoemestrin C exerts rapid and prominent anti-breast cancer effect in triple-negative breast cancer by inducing SLX4 and YAP degradation.Acta pharmacologica Sinica · 2026Article
- Kremen1 dependence receptor induces SEC24C and ATG9A-dependent cell death.Cell communication and signaling : CCS · 2026Article
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- Targeting Autophagy, Ferroptosis, and Neuroinflammation: Polyphenol-Mediated Modulation of Emerging Signaling Pathways in Neurodegeneration.Molecular neurobiology · 2026Review
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
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- Hypermethylation of lysosomal-associated genes LAMP1 and LAMP2 compromises lysosome function in patients with acute lymphoblastic leukemia.Immunologic research · 2025Article
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- Sequelae and reversal of age-dependent alterations in mitochondrial dynamics via autophagy enhancement in reprogrammed human neurons.bioRxiv : the preprint server for biology · 2025Article
- The elucidation of the dual role of Beclin-1 in ischemic stroke through systems biology modeling.iScience · 2025Article
- The Link Between Endoplasmic Reticulum Stress and Lysosomal Dysfunction Under Oxidative Stress in Cancer Cells.Biomolecules · 2025Review
- Cell-Specific Vulnerability of Human Glioblastoma and Astrocytoma Cells to Mephedrone-An In Vitro Study.Molecules (Basel, Switzerland) · 2025Article
- β-Catenin/c-Myc Axis Modulates Autophagy Response to Different Ammonia Concentrations.Advanced biology · 2025Article
- Let's talk about flux: the rising potential of autophagy rate measurements in disease.Autophagy · 2024Article
- Inhibitory Effect of Alnustone on Survival and Lung Metastasis of Colorectal Cancer Cells.Nutrients · 2024Article
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Autophagy comprises the processes of autophagosome synthesis and lysosomal degradation. In certain stress conditions, increased autophagosome synthesis may be associated with decreased lysosomal activity, which may result in reduced processing of the excessive autophagosomes by the rate-limiting lysosomal activity. Thus, the excessive autophagosomes in such situations may be largely unfused to lysosomes, and their formation/accumulation under these conditions is assumed to be futile for autophagy. The role of cytotoxicity in accumulating autophagosomes (representing synthesis of autophagosomes subsequently unfused to lysosomes) has not been investigated previously. Here, we found that accumulation of autophagosomes compromised cell viability, and this effect was alleviated by depletion of autophagosome machinery proteins. We tested whether reduction in autophagosome synthesis could affect cell viability in cell models expressing mutant huntingtin and α-synuclein, given that both of these proteins cause increased autophagosome biogenesis and compromised lysosomal activity. Importantly, partial depletion of autophagosome machinery proteins Atg16L1 and Beclin 1 significantly ameliorated cell death in these conditions. Our data suggest that production/accumulation of autophagosomes subsequently unfused to lysosomes (or accumulation of autophagosomes) directly induces cellular toxicity, and this process may be implicated in the pathogenesis of neurodegenerative diseases. Therefore, lowering the accumulation of autophagosomes may represent a therapeutic strategy for tackling such 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.