Multilayered Control of Protein Turnover by TORC1 and Atg1

Zehan Hu, Serena Raucci, Malika Jaquenoud, Riko Hatakeyama, Michael Stumpe, Rudolf Rohr, Fulvio Reggiori, Claudio De Virgilio, Jörn Dengjel* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)
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The target of rapamycin complex 1 (TORC1) is a master regulator of cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy target is Atg13, a subunit of the Atg1 kinase complex that acts as the gatekeeper of canonical autophagy. To study whether the activities of TORC1 and Atg1 are coupled through additional, more intricate control mechanisms than simply this linear pathway, we analyzed the epistatic relationship between TORC1 and Atg1 by using quantitative phosphoproteomics. Our in vivo data, combined with targeted in vitro TORC1 and Atg1 kinase assays, not only uncover numerous TORC1 and Atg1 effectors, but also suggest distinct bi-directional regulatory feedback loops and characterize Atg29 as a commonly regulated downstream target of both TORC1 and Atg1. Thus, an exquisitely multilayered regulatory network appears to coordinate TORC1 and Atg1 activities to robustly tune autophagy in response to nutritional cues.

Original languageEnglish
Pages (from-to)3486-3496.e6
Number of pages18
JournalCell Reports
Issue number13
Early online date24 Sept 2019
Publication statusPublished - 24 Sept 2019
Externally publishedYes

Bibliographical note

This research was generously supported by the Canton of Fribourg and the Swiss National Science Foundation (J.D., C.D.V., and R.R.) and by TRANSAUTOPHAGY, COST Action CA15138 (J.D. and F.R.). F.R. is supported by ZonMW VICI (016.130.606), ZonMW TOP (91217002), ALW Open Programme (ALWOP.310), Marie Skłodowska-Curie Cofund (713660), and Marie Skłodowska Curie ETN (765912) grants.


  • autophagy
  • metabolism
  • kinase
  • phosphorylation
  • mass spectrometry
  • proteomics
  • Atg29
  • signaling


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