Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes
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A cellular compartment allows simultaneous protein synthesis and degradation.
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OIS is associated with accumulation of autolysosome compartments, where Rag GTPase-dependent sequestration of mTOR correlates with enhanced autophagosome formation and cytokine production.
“Interestingly, OIS is associated with accumulation of autolysosome compartments, where a Rag GTPase-dependent sequestration of mTOR correlates with enhanced autophagosome formation as well as cytokine production (Narita et al. 2011).”
From Cellular senescence and its effector programs (2014) · cites this paper as Narita et al. 2011
The paper reports autolysosome enrichment during Ras-induced senescence and shows that RagB disruption reduces mTOR enrichment in the TASCC and IL-6/8 production (passages [1] and [3]; page unavailable). It places developing autophagosomes outside the TASCC and suggests that this spatial arrangement allows simultaneous activity, but does not show that Rag-dependent mTOR sequestration correlates with enhanced autophagosome formation. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSubcellular localization of autophagy and mTOR might play a key role for simultaneous activation of anabolic and catabolic processes during senescence.
“We recently showed that the subcellular localization of autophagy and mTOR might play a key role for the simultaneous activation of anabolic and catabolic processes during senescence (Narita et al. 2011).”
From Cellular senescence and its effector programs (2014) · cites this paper as Narita et al. 2011
Autophagy has been implicated in establishing the SASP through the TOR autophagy spatial coupling compartment (TASCC).
“macro-autophagy (hereafter referred to as autophagy)—a tightly regulated major lysosomal degradation pathway (27–30)—has been implicated in establishing the SASP through the target of rapamycin (TOR) autophagy spatial coupling compartment (TASCC).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [32]
Autophagy is both a negative and a positive regulator of senescence, resolving apparently contradictory reports in the literature.
“Our results indicate that autophagy is both a negative and a positive regulator of senescence, resolving apparently contradictory reports in the literature (31–33, 44).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [32]
Autophagy is dynamically activated during OIS and facilitates synthesis of IL-6 and IL-8, major SASP components.
“Autophagy is dynamically activated during OIS and facilitates the synthesis of interleukin 6 (IL-6) and IL-8, major components of the SASP 58,59 .”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [58]
The TASCC, close to the nucleus, is highly enriched in mTOR and keeps mTOR away from the autophagy machinery to avoid its inactivation.
“The mTOR–autophagy spatial coupling compartment (TASCC), which is close to the nucleus, is highly enriched in mTOR and keeps mTOR away from the autophagy machinery, located away from the TASCC, to avoid its inactivation.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [246]
The simultaneous activation of mTOR and autophagy in oncogenic Ras-induced senescence is possible through spatiotemporal sub-compartmentalization of mTOR and autophagy.
“This paradoxical outcome is possible through the spatiotemporal sub-compartmentalization of mTOR and autophagy that allows their simultaneous activation [246].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [246]
Recycled amino acids are used by mTOR to support increased biosynthetic demand during acquisition of the OIS phenotype.
“These amino acids are then used by mTOR to support the increased biosynthetic demand during the acquisition of the OIS phenotype [246].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [246]
Selective autophagy of GATA4, which accumulates during senescence induction, can prevent senescence.
“Conversely, selective autophagy, for instance of GATA4 that accumulates during senescence induction [160], can prevent senescence [160,246].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [246]
In the TASCC, mTOR is closely associated with lysosomes/autolysosomes that generate a high flux of recycled amino acids and other metabolites.
“In the TASCC, mTOR is closely associated with lysosomes/autolysosomes that generate a high flux of recycled amino acids and other metabolites.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [246]
TASCCs allow simultaneous activation of anabolic and catabolic processes, facilitating mTOR-controlled synthesis of secretory proteins with energy or building blocks from constitutive autophagy.
“TASCCs provide cells with a mechanism for simultaneous activation of anabolic and catabolic processes, which facilitates mTOR-controlled synthesis of secretory proteins with sources of energy or building blocks provided by constitutive autophagy”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [53]
Podocytes form TASCCs, cytoplasmic compartments enriched for mTORC1 that include autolysosomes but largely exclude autophagosomes.
“podocytes form TOR–autophagy spatial coupling compartments (TASCCs), which are distinct cytoplasmic compartments enriched for mTORC1 that include autolysosomes but largely exclude autophagosomes”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [53]
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“In turn, mTORC1 (mTOR Complex 1) promotes the utilization of these metabolites for the synthesis of the SASP components (Narita et al., 2011).”
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- Authors
- Narita, M., Young, A. R. J., Arakawa, S., Samarajiwa, S. A., Nakashima, T., Yoshida, S., Hong, S., Berry, L. S., Reichelt, S., Ferreira, M., Tavaré, S., Inoki, K., Shimizu, S., & Narita, M.
- Affiliations
- Cancer Research UK (GB)
- Tokyo Medical and Dental University (JP)
- University of Cambridge (GB)
- University of Michigan (US)
- Corresponding author
- Narita, Masako
- Young, Andrew R. J.
- Narita, Masashi
- ORCID
- Venue
- Science
- Published
- 2011-05-20
- Volume
- 332
- Issue
- 6032
- Pages
- 966-970
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3426290
- OpenAlex
- W1965493795
- Cited by
- 594
- References
- 26
- Citations by year
- 2026: 30 · 2025: 26 · 2024: 41 · 2023: 40 · 2022: 52 · 2021: 50 · 2020: 39 · 2019: 38 · 2018: 36 · 2017: 28 · 2016: 37 · 2015: 31 · 2014: 36 · 2013: 44 · 2012: 45
- FWCI
- 35.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK083491)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- mTOR, autophagy, spatial coupling, Golgi apparatus, lysosomes, Ras-induced senescence, Rag GTPases, amino acid signaling, protein secretion, interleukin-6, interleukin-8, macrophage differentiation, glomerular podocytes, protein turnover
- MeSH terms
- Amino Acids, Animals, Autophagy, Cell Line, Cytoplasm, Golgi Apparatus, Humans, Lysosomes, Phagosomes, Phenotype, Proteins, Genes, ras, Protein Biosynthesis, Vacuoles, Nocodazole, Interleukin-6, Interleukin-8, Cellular Senescence, Endoplasmic Reticulum, Rough, HL-60 Cells, Monomeric GTP-Binding Proteins, trans-Golgi Network, Cytoplasmic Vesicles, Podocytes, Mice, TOR Serine-Threonine Kinases
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