Autophagosome assembly and cargo capture in the distal axon
Open accessAbstract
Autophagy is an essential lysosomal degradation pathway in neurons, yet the basic mechanisms involved are poorly understood. Here, we discuss our recent study in which we define autophagosome dynamics in primary neurons. We find that autophagosomes initiate at the distal tip of the axon in primary neurons and undergo retrograde transport toward the cell soma. As they move distally to proximally along the axon, autophagosomes mature and become increasingly acidified, consistent with the formation of an autolysosomal compartment that may more effectively catalyze the degradation of enveloped cargo. Our findings suggest that autophagosome biogenesis and maturation is a constitutive process in primary neurons that is temporally and spatially regulated along the axon.
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Newly-formed autophagosomes in neuronal processes undergo retrograde transport to the soma and proximal segments of neurites to fuse with somatodendritic lysosomes for cargo degradation, with maturation and acidification of the autophagosomal lumen developing en passant.
“Newly-formed autophagosomes in neuronal processes undergo retrograde transport to the soma and proximal segments of neurites to fuse with somatodendritic lysosomes for cargo degradation, with maturation and acidification of the autophagosomal lumen developing en passant [370,372,374].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [374]
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Autophagy as a promoter of longevity: insights from model organisms
Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“neurites to fuse with somatodendritic lysosomes for cargo degradation, with maturation and acidification of the autophagosomal lumen developing en passant [370,372,374].”
Background
- Authors
- Maday, S., & Holzbaur, E. L. F.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Holzbaur, Erika L.F.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2012-05-13
- Volume
- 8
- Issue
- 5
- Pages
- 858-860
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3378425
- OpenAlex
- W2000319343
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 2 · 2013: 1
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS060698)
- National Institute of Neurological Disorders and Stroke (R37NS060698, NS060698, R01NS060698)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagosome formation, autophagosome maturation, retrograde transport, axons, distal axons, primary neurons, autolysosomes, lysosomal degradation
- MeSH terms
- Animals, Autophagy, Axons, Biological Transport, Humans, Lysosomes, Mitochondria, Models, Biological, Phagosomes
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