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08:35

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Published on: June 12, 2017

Spatio-temporal association between mTOR and autophagy during cellular senescence

Andrew R J Young1, Masako Narita, Masashi Narita

  • 1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.

Autophagy
|July 30, 2011
PubMed

Insights

Lysosomes spatially link the mechanistic target of rapamycin (mTOR) and autophagy, forming a compartment that enhances protein synthesis and lysosome biogenesis during senescence. This TOR-autophagy spatial coupling compartment (TASCC) supports secretory functions and promotes autophagy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Emerging evidence links lysosomes to the mechanistic target of rapamycin (mTOR) signaling pathway.
  • mTOR is recruited to lysosomal surfaces in response to amino acids, but its biological significance remains unclear.
  • Lysosomes play a role in cellular senescence and are implicated in regulating mTOR activity.

Purpose of the Study:

  • To investigate the spatial relationship between lysosomes, mTOR, and autophagy during oncogenic Ras-induced senescence.
  • To elucidate the functional significance of the TOR-autophagy spatial coupling compartment (TASCC).
  • To understand how TASCC formation influences protein synthesis, lysosome biogenesis, and autophagy.

Main Methods:

  • Cellular imaging techniques to visualize lysosomes, mTOR, and autophagic structures.
  • Biochemical assays to measure protein synthesis and mTOR activity.
  • Genetic manipulation to study the role of Rag GTPases and Rheb in TASCC formation.

Main Results:

  • Lysosomes spatially couple mTOR and autophagy, forming a TASCC near the Golgi apparatus during senescence.
  • The TASCC is enriched for autolysosomes and facilitates mTOR recruitment and activation.
  • mTOR recruitment to the TASCC enhances protein synthesis and reinforces lysosome and autophagy biogenesis.
  • TASCC formation supports the production of secretory proteins and promotes autophagy by sequestering mTOR.

Conclusions:

  • The TASCC is a novel cellular compartment that spatially integrates mTOR signaling and autophagy.
  • TASCC formation is a self-enhancing process that promotes cellular functions like protein synthesis and lysosome biogenesis.
  • Understanding TASCC biology offers insights into senescence, cancer, and metabolic regulation.

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