The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy
Open accessAbstract
SUMMARY Chaperone-mediated autophagy (CMA), a selective form of degradation of cytosolic proteins in lysosomes, contributes to maintenance of proteostasis and to the cellular adaptation to stress. CMA substrates are delivered by a cytosolic chaperone to the lysosomal surface, where upon unfolding, are internalized through a membrane translocation complex. The molecular components that participate in CMA substrate targeting and translocation are well characterized but those involved in CMA regulation remain mostly unknown. In this study, we have identified that CMA is under the positive control of the phosphatase PHLPP1 that associates with the lysosomal membrane and counteracts the inhibitory effect of mTORC2 on CMA. Lysosomal Akt, a target of the mTORC2/PHLPP1 kinase-phosphatase pair, modulates CMA activity by controlling the dynamics of assembly and disassembly of the CMA translocation complex at the lysosomal membrane. The lysosomal mTORC2/PHLPP1/Akt axis could become a target to restore CMA dysfunction in aging and disease.
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Cites
Autophagy fights disease through cellular self-digestion
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Self-citationPhosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
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Autophagy and the Integrated Stress Response
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“Although different GTPases mediate lysosomal association of TORC (Sancak et al., 2010), and Rac1 has shown a positive regulatory effect for mTORC2 in some cells (Saci et al.”
InfluentialAkt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation
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Self-citationRegulation of TOR by small GTPases
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“Immunoblot for different GTPases previously described to modulate TORC (Duran and Hall, 2012) demonstrated that Rac1, Rheb, RagD and RagB were all present in CMA-active and inactive lysosomes although with different abundance (Fig.”
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
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Self-citationMolecular definitions of autophagy and related processes
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Self-citationThe coming of age of chaperone-mediated autophagy
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Self-citationThe Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective
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Metadata
- Authors
- Arias, E., Koga, H., Diaz, A., Mocholi, E., Patel, B., & Cuervo, A. M.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 59
- Issue
- 2
- Pages
- 270-284
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1493534235
- Cited by
- 280
- References
- 7
- FWCI
- 18.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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