Phagosome resolution regenerates lysosomes and maintains the degradative capacity in phagocytes
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Abstract
Phagocytes engulf unwanted particles into phagosomes that then fuse with lysosomes to degrade the enclosed particles. Ultimately, phagosomes must be recycled to help recover membrane resources that were consumed during phagocytosis and phagosome maturation, a process referred to as “phagosome resolution.” Little is known about phagosome resolution, which may proceed through exocytosis or membrane fission. Here, we show that bacteria-containing phagolysosomes in macrophages undergo fragmentation through vesicle budding, tubulation, and constriction. Phagosome fragmentation requires cargo degradation, the actin and microtubule cytoskeletons, and clathrin. We provide evidence that lysosome reformation occurs during phagosome resolution since the majority of phagosome-derived vesicles displayed lysosomal properties. Importantly, we show that clathrin-dependent phagosome resolution is important to maintain the degradative capacity of macrophages challenged with two waves of phagocytosis. Overall, our work suggests that phagosome resolution contributes to lysosome recovery and to maintaining the degradative power of macrophages to handle multiple waves of phagocytosis.
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Efficient degradation of phagocytic cargo sustains phagocytic uptake in macrophages.
“Efficient degradation of phagocytic cargo sustains phagocytic uptake in macrophages71,72.”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [71]
The Discussion section, “Cargo degradation in phagolysosome resolution” (page unavailable), says cargo degradation is required for phagosome resolution. The Results section, “Clathrin-mediated phagosome fragmentation is required to recover degradative capacity” (page unavailable), shows that macrophages recover the ability to degrade cargo in subsequent phagosomes. It does not establish that efficient degradation sustains the uptake or engulfment of new cargo. (LLM, conf=0.83)
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- Authors
- Lancaster, C. E., Fountain, A., Dayam, R. M., Somerville, E., Sheth, J., Jacobelli, V., Somerville, A., Terebiznik, M. R., & Botelho, R. J.
- Affiliations
- University of Toronto (CA)
- Toronto Metropolitan University (CA)
- Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada 3
- Corresponding author
- Terebiznik, Mauricio R.
- Botelho, Roberto J.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2021-06-28
- Volume
- 220
- Issue
- 9
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC8241537
- OpenAlex
- W3173868070
- Cited by
- 77
- References
- 4
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 17 · 2023: 19 · 2022: 9 · 2021: 5 · 2020: 1
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Council of Canada (RGPIN-2018-05734, RGPAS-2018-522692)
- Canadian Institutes of Health Research (123373)
- Canada Research Chairs
- Government of Ontario (ER13-09-042)
- Ryerson University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phagolysosomes, macrophages, phagocytosis, membrane fission, vesicle budding, clathrin, actin cytoskeleton, microtubules, phagosome maturation
- MeSH terms
- RAW 264.7 Cells, Actins, Animals, Clathrin, Escherichia coli, Lysosomes, Membrane Fusion, Actin Cytoskeleton, Microtubules, Phagocytosis, Phagosomes, Gene Expression, Genes, Reporter, Green Fluorescent Proteins, Mice, Proteolysis
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