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Multiplexed suppression of TOR complex 1 induces autophagy during starvation

Tomoyuki Fukuda1, Kazuhiro Shiozaki2,3

  • 1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Autophagy
|June 4, 2021
PubMed

Insights

Fission yeast and mammals utilize conserved signaling pathways differently to control cell growth and autophagy. Key regulators like GATOR1 and GATOR2 exhibit distinct roles in nutrient sensing and TORC1 pathway regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Target of rapamycin complex 1 (TORC1) is a central regulator of cell growth, anabolism, and autophagy.
  • In mammals, amino acid starvation inactivates TORC1 via the GATOR1 and GATOR2 complexes.
  • Understanding nutrient-sensing pathways is crucial for metabolic and cellular regulation.

Purpose of the Study:

  • To investigate the roles of conserved TORC1 regulatory complexes (GATOR1 and GATOR2) in fission yeast.
  • To compare the mechanisms of TORC1 regulation by nutrient availability between fission yeast and mammals.
  • To elucidate the distinct utilization of signaling modules in different organisms.

Main Methods:

  • Genetic analysis in fission yeast (Schizosaccharomyces pombe).
  • Biochemical assays to study protein complex interactions.
  • Nutrient starvation and nitrogen source deprivation experiments.
  • Monitoring of TORC1 activity and autophagy induction.

Main Results:

  • Fission yeast Sea3, a GATOR2 component, unexpectedly functions within the GATOR1 complex to suppress TORC1.
  • Fission yeast GATOR1 is not involved in amino acid starvation-induced TORC1 attenuation, which is Gcn2-dependent.
  • Nitrogen starvation suppresses TORC1 in fission yeast via GATOR1 and the Tsc1-Tsc2 complex.

Conclusions:

  • Conserved signaling modules controlling TORC1 activity and autophagy are differentially employed in fission yeast and mammals.
  • Fission yeast exhibits unique mechanisms for nutrient sensing and TORC1 regulation compared to mammals.
  • This study highlights the evolutionary divergence in fundamental cellular regulatory pathways.
Keywords:
AutophagyGATOR complexGcn2RAG GTPaseTORTSC complex

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