mTOR regulates phagosome and entotic vacuole fission
Open accessAbstract
Macroendocytic vacuoles formed by phagocytosis, or the live-cell engulfment program entosis, undergo sequential steps of maturation, leading to the fusion of lysosomes that digest internalized cargo. After cargo digestion, nutrients must be exported to the cytosol, and vacuole membranes must be processed by mechanisms that remain poorly defined. Here we find that phagosomes and entotic vacuoles undergo a late maturation step characterized by fission, which redistributes vacuolar contents into lysosomal networks. Vacuole fission is regulated by the serine/threonine protein kinase mammalian target of rapamycin complex 1 (mTORC1), which localizes to vacuole membranes surrounding engulfed cells. Degrading engulfed cells supply engulfing cells with amino acids that are used in translation, and rescue cell survival and mTORC1 activity in starved macrophages and tumor cells. These data identify a late stage of phagocytosis and entosis that involves processing of large vacuoles by mTOR-regulated membrane fission.
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Lysosomal degradation of internalized entotic cells generates nutrients recovered by engulfing cells via a mechanism involving PIKFYVE.
“the lysosomal degradation of internalized entotic cells generates nutrients that are recovered by engulfing cells, via a mechanism that reportedly involves phosphoinositide kinase, FYVE-type zinc finger containing (PIKFYVE) [704, 707, 708].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [707]
Free amino acids can be recovered from engulfment and digestion of entire living cells via entosis and from phagocytosis of apoptotic corpses.
“free amino acids can be recovered from the engulfment and digestion of entire living cells via a process known as entosis (Figure 3B), as well as from phagocytosis of apoptotic cellular corpses”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Krajcovic et al., 2013
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References 35 · Cited by 149
- Authors
- Krajcovic, M., Krishna, S., Akkari, L., Joyce, J. A., & Overholtzer, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Overholtzer, Michael
- Venue
- Molecular Biology of the Cell
- Published
- 2013-12
- Volume
- 24
- Issue
- 23
- Pages
- 3736-3745
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC3842999
- OpenAlex
- W2099999066
- Cited by
- 149
- References
- 35
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 23 · 2022: 13 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 17 · 2017: 11 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 1
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA177697, R21CA177697, U54CA148967, CA148967, P30CA008748)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTORC1, phagosome maturation, entosis, membrane fission, lysosome fusion, nutrient cycling, amino acid uptake, cancer cells, kinase regulation
- MeSH terms
- Amino Acids, Animals, Cell Line, Humans, Lysosomes, Membrane Fusion, Models, Biological, Phagocytosis, Phagosomes, Vacuoles, Mice, Entosis, TOR Serine-Threonine Kinases
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