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Multilayered Control of Protein Turnover by TORC1 and Atg1

Zehan Hu1, Serena Raucci1, Malika Jaquenoud1

  • 1Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.

Cell Reports
|September 26, 2019
PubMed

Insights

The target of rapamycin complex 1 (TORC1) and Atg1 kinase complex activities are intricately linked, revealing complex regulatory feedback loops. This multilayered network robustly tunes autophagy in response to nutritional cues.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of rapamycin complex 1 (TORC1) is a key regulator of cellular homeostasis, controlling anabolic and catabolic processes.
  • Autophagy, a major catabolic process, is tightly regulated, with Atg13 identified as a critical target of TORC1 and a gatekeeper of canonical autophagy.

Purpose of the Study:

  • To investigate intricate coupling mechanisms between TORC1 and Atg1 kinase activities beyond the linear pathway.
  • To elucidate the complex regulatory network governing autophagy.

Main Methods:

  • Quantitative phosphoproteomics was employed to analyze the epistatic relationship between TORC1 and Atg1.
  • In vivo data were complemented by targeted in vitro TORC1 and Atg1 kinase assays.

Main Results:

  • Numerous downstream effectors of both TORC1 and Atg1 were identified.
  • Distinct bi-directional regulatory feedback loops between TORC1 and Atg1 were uncovered.
  • Atg29 was characterized as a downstream target regulated by both TORC1 and Atg1.

Conclusions:

  • A complex, multilayered regulatory network coordinates TORC1 and Atg1 activities.
  • This network robustly tunes autophagy in response to nutritional cues, ensuring cellular homeostasis.
Keywords:
Atg29autophagykinasemass spectrometrymetabolismphosphorylationproteomicssignaling

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