Spatial coupling of mTOR and autophagy augments secretory phenotypes
What this study shows
Protein synthesis and autophagic degradation are usually described as opposites that mTOR switches between, and this paper shows a compartment where the cell deliberately runs both at once. In senescent cells, autolysosomes and mTOR gather at one side of the Golgi (the TASCC), mTOR gets there in an amino-acid- and Rag-dependent way, and destroying that arrangement cuts interleukin-6/8 secretion. Boundary: cells, not organisms; it explains how the senescent secretory programme is fuelled, not whether blocking it helps an animal.
Abstract
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Protein synthesis and autophagic degradation are regulated in an opposite manner by mammalian target of rapamycin (mTOR), whereas under certain conditions it would be beneficial if they occurred in unison to handle rapid protein turnover. We observed a distinct cellular compartment at the trans side of the Golgi apparatus, the TOR-autophagy spatial coupling compartment (TASCC), where (auto)lysosomes and mTOR accumulated during Ras-induced senescence.
Read the full abstract on PubMed →At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human and mouse cells (Ras-induced senescent fibroblasts, macrophages, podocytes)) 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 | Human and mouse cells (Ras-induced senescent fibroblasts, macrophages, podocytes) |
| Journal | Science |
| Year | 2011 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1126/science.1205407 · PMID 21512002 |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Pathway relations
Supports
mTORC1 activates Senescence-associated secretory phenotype (SASP)Strongest evidence: A (Animal model) · emerging, few independent studies · Status: Proposed
plausible in people, not shown directly
Three studies, all in cells or a rat disease model. LAB2015 and NAR2011 measure the secretory output of cells that are already senescent (IL1A translation; IL-6/IL-8 production fuelled by mTOR at the TASCC). CHEN2026C (human disc cells,…
Supports
Rag GTPases recruits mTORC1Strongest evidence: A (Animal model) · settled in the literature · Status: Proposed
plausible in people, not shown directly
Rag paralogues are not interchangeable: RagC/D sets substrate specificity downstream (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding, while both Rags are involved for non-lysosomal substrates like S6K), and RagA/B sets…
People in the Atlas
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Discovered, as first author, the TASCC, a compartment in senescent cells where mTOR and autophagy work side by side to fuel the secretion of inflammatory proteins
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Studies what senescent cells do to the tissue around them, and showed that mTOR position, not just mTOR activity, sets their secretory output
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First-authored the cryo-EM structure identifying TM6SF1 as a lysosomal cholesterol-binding protein involved in regulating mTORC1 signalling
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Showed as a postdoc in Kun-Liang Guan's lab that Akt switches off TSC2, that TSC2 is the off-switch (GAP) for the small GTPase Rheb, and that AMPK and GSK3 feed energy and Wnt signals into the same brake. His Michigan lab studies mTOR signalling in metabolism and kidney disease
More: 10 other authors
No profile yet: Young AR, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, Berry LS, Reichelt S, Ferreira M, Tavare S, Shimizu S
Related studies
- M Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism
WAN2017 · 2017 · Shares: Cellular senescence, Autophagy, Senescence-associated secretory phenotype (SASP)
- S Therapeutic reversal of cellular senescence: A systematic review of senolytics, senomorphics and anti-ageing therapies in human clinical trials
TRI2026 · 2026 · Shares: mTOR, Cellular senescence, Senescence-associated secretory phenotype (SASP)
- A Dioscorea polystachya Turcz. attenuates male reproductive aging through modulation of mTOR-Beclin-1-mediated autophagy in Leydig and Sertoli cells
ZHANG2026B · 2026 · Shares: mTOR, Cellular senescence, Autophagy
- A Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation
CHEN2026C · 2026 · Shares: Cellular senescence, Senescence-associated secretory phenotype (SASP)
- M mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation
LAB2015 · 2015 · Shares: Cellular senescence, Senescence-associated secretory phenotype (SASP)
More related studies
- R The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease
GOU2023 · 2023 · Shares: Lysosome, Rag GTPases
- M A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids
GOL2022 · 2022 · Shares: Lysosome, Rag GTPases
- M Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2
DEM2014 · 2014 · Shares: Lysosome, Rag GTPases
- M Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes
MAR2013 · 2013 · Shares: Lysosome, Rag GTPases
- M SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling
KIM2012 · 2012 · Shares: Lysosome, Rag GTPases
- M mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase
ZON2011 · 2011 · Shares: Lysosome, Rag GTPases
- M Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids
SAN2010 · 2010 · Shares: Lysosome, Rag GTPases
- A Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK
YAN2026B · 2026 · Shares: Cellular senescence, Autophagy
Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Disruption of mTOR localisation to the TASCC; amino-acid and Rag GTPase manipulation |
| Target | mTOR spatial coupling with autolysosomes (TASCC); SASP (IL-6/IL-8) |
| Model | Human and mouse cells (Ras-induced senescent fibroblasts, macrophages, podocytes) |
| Effect | Co-localising mTOR with autolysosomes at the trans-Golgi supports mass synthesis of secreted proteins; disrupting it reduces IL-6/8 synthesis. |
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