ArticleMolecular biology of the cell2022
Spatiotemporal analysis of axonal autophagosome-lysosome dynamics reveals limited fusion events and slow maturation.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Microglia extract neuronal proteolytic organelles via skoupocytosis.bioRxiv : the preprint server for biology · 2026Article
- KIF1A-mediated trafficking is required for neuronal autophagy in human neurons.bioRxiv : the preprint server for biology · 2026Article
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation.Cell reports · 2026Article
- Diffusive spreading across dynamic mitochondrial network architectures.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.Nature communications · 2026Article
- MYO5A-mediated stabilization promotes the acquisition of fusion competence in sealed autophagosomes.The EMBO journal · 2026Article
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Article
- Sequelae and reversal of age-dependent alterations in mitochondrial dynamics via autophagy enhancement in reprogrammed human neurons.bioRxiv : the preprint server for biology · 2025Article
- Start early and pack light: Collaborative adventures in theory and experiment.Seminars in cell & developmental biology · 2025Review
- Autophagy Modulation by Antidepressants: Mechanisms and Implications.Neurochemical research · 2025Review
- Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.Nature communications · 2025Article
- Autophagic stress activates distinct compensatory secretory pathways in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of LRRK2 in axonal transport and Parkinson's disease.The Biochemical journal · 2025Review
- Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.The Journal of cell biology · 2025Article
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal.Autophagy · 2024Article
- Article
- Article
- The role of PI3K signaling pathway in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Macroautophagy is a homeostatic process required to clear cellular waste. Neuronal autophagosomes form constitutively in the distal tip of the axon and are actively transported toward the soma, with cargo degradation initiated en route. Cargo turnover requires autophagosomes to fuse with lysosomes to acquire degradative enzymes; however, directly imaging these fusion events in the axon is impractical. Here we use a quantitative model, parameterized and validated using data from primary hippocampal neurons, to explore the autophagosome maturation process. We demonstrate that retrograde autophagosome motility is independent of fusion and that most autophagosomes fuse with only a few lysosomes during axonal transport. Our results indicate that breakdown of the inner autophagosomal membrane is much slower in neurons than in nonneuronal cell types, highlighting the importance of this late maturation step. Together, rigorous quantitative measurements and mathematical modeling elucidate the dynamics of autophagosome-lysosome interaction and autophagosomal maturation in the axon.
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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.