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Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Tor directly controls the Atg1 kinase complex to regulate autophagy

Yoshiaki Kamada1, Ken-ichi Yoshino, Chika Kondo

  • 1Division of Molecular Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan. yoshikam@nibb.ac.jp

Molecular and Cellular Biology
|December 10, 2009
PubMed

Insights

Autophagy, essential for cell survival, is regulated by Tor complex1 (TORC1). This study reveals TORC1 directly phosphorylates Atg13, a key autophagy protein, controlling the process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a crucial cellular degradation process vital for survival under starvation.
  • Nutrient deprivation induces autophagy by inactivating the Tor complex1 (TORC1), a key regulator of cell growth.
  • The precise mechanism of TORC1-mediated autophagy regulation and its direct targets are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which TORC1 controls autophagy.
  • To identify the direct target of TORC1 activity in the autophagy pathway.
  • To investigate the role of Atg13 phosphorylation in TORC1-mediated autophagy.

Main Methods:

  • Investigated the interaction between TORC1 and Atg13 in yeast.
  • Utilized site-directed mutagenesis to create an unphosphorylatable Atg13 mutant.
  • Assessed autophagy induction and Atg1 activation under nutrient-rich conditions using the Atg13 mutant.

Main Results:

  • Demonstrated that yeast TORC1 directly phosphorylates Atg13 at multiple serine residues.
  • Showed that an Atg13 mutant, unable to be phosphorylated, bypasses TORC1 inhibition.
  • Observed that this unphosphorylatable Atg13 mutant induces autophagy and activates Atg1 even in nutrient-rich conditions.

Conclusions:

  • TORC1 directly regulates autophagy by phosphorylating Atg13, a component upstream of the Atg1 kinase complex.
  • Phosphorylation of Atg13 by TORC1 is a critical step in suppressing autophagy under nutrient-rich conditions.
  • Targeting Atg13 phosphorylation offers a potential mechanism for controlling autophagy induction.

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