The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
mTOR activates the VPS 34– UVRAG complex to regulate autolysosomal tubulation and cell survival
Open accessAbstract
Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrient-sensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome-lysosome reformation (ALR). Here we identify a lysosomal pool of phosphatidylinositol 3-phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3-kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process.
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Citations
Cites
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 1×
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Self-citationPhosphoinositides in cell regulation and membrane dynamics
Di Paolo, G., & De Camilli, P. (2006) · Nature · doi:10.1038/nature05185 · Cited by 2,790
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“Indeed, this is where active mTOR is localised (Sancak et al , 2010; Betz & Hall, 2013), and as we now show here, UVRAG too. mTOR and VPS34 have a complex relationship, and multiple studies have shown that nutrient starvation, and inhibition of mTOR, reduce total cellular PI(3)P levels (Byfield et…”
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076
ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery
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Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG
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The lysosome: from waste bag to potential therapeutic target
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Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury
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“In support of this, we found that dblA-expressing cells were much more sensitive to lysosomal damage caused by the lysosomotropic reagent L-leucyl-L-leucine methyl ester (LLOMe, Maejima et al , 2013).”
Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationPhosphoinositides as membrane organizers
Posor, Y., Jang, W., & Haucke, V. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00490-x · Cited by 469
The interplay of ROS and the PI3K/Akt pathway in autophagy regulation
Kma, L., & Baruah, T. J. (2022) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.2104 · Cited by 394
Digesting the Expanding Mechanisms of Autophagy
Ktistakis, N. T., & Tooze, S. A. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.03.006 · Cited by 367
Metadata
- Authors
- Munson, M. J., Allen, G. F., Toth, R., Campbell, D. G., Lucocq, J. M., & Ganley, I. G.
- Venue
- The EMBO Journal
- Published
- 2015-07-02
- Volume
- 34
- Issue
- 17
- Pages
- 2272-2290
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2135453787
- Cited by
- 168
- References
- 11
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Munson, M. J., Allen, G. F., Toth, R., Campbell, D. G., Lucocq, J. M., & Ganley, I. G. (2015). mTOR activates the VPS 34– UVRAG complex to regulate autolysosomal tubulation and cell survival. The EMBO Journal. https://doi.org/10.15252/embj.201590992
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