Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy

Arias E, Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM · 2015 · Mol Cell · Atlas ID ARI2015

What this study shows

Extends the mTOR-autophagy relationship to a third form of autophagy that the Atlas otherwise does not cover, and reverses two of its usual terms. Here it is mTORC2, not mTORC1, that sits on the lysosomal membrane, and it inhibits chaperone-mediated autophagy through Akt, while the phosphatase PHLPP1 counteracts it; the balance controls assembly and disassembly of the translocation complex that pulls single proteins into the lysosome. Boundary: mechanism in cells and rodent liver; the claim that restoring this axis helps in ageing or disease is proposed, not tested here.

Abstract

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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, they 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.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse liver, rat liver, cell lines (NIH 3T3)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mouse liver, rat liver, cell lines (NIH 3T3)
Journal	Mol Cell
Year	2015
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1016/j.molcel.2015.05.030 · PMID 26118642

Cite this paper

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Arias, E., Koga, H., Diaz, A., Mocholi, E., Patel, B., & Cuervo, A. M. (2015). Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy. Mol Cell. https://doi.org/10.1016/j.molcel.2015.05.030

@article{ARI2015,
  author       = {Arias, E. and Koga, H. and Diaz, A. and Mocholi, E. and Patel, B. and Cuervo, A. M.},
  title        = {{Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy}},
  journal      = {Mol Cell},
  year         = {2015},
  doi          = {10.1016/j.molcel.2015.05.030},
  note         = {PMID: 26118642},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ARI2015) [Data set]. https://mtor-atlas.org/study/ARI2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ARI2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ARI2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ARI2015/},
  doi          = {10.5281/zenodo.22059963}
}