page_title: Atg1
section_title: Regulation
hierarchical_section_title: Atg1 / Regulation
caption_attribution_description: English: Mechanism of Atg1 complex regulation in yeast by phosphorylation of Atg13 by TOR kinase under nutrient rich conditions. The resulting phosphorylation leads to a dissociation of Atg1 and Atg13 and hence a breakdown of the complex.
context_page_description: AuTophaGy related 1 is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1.
  It is essential for the initial building of the autophagosome and Cvt vesicles.
  In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability.
context_section_description: The autophagy machinery is activated upon several stimuli, like nutrient starvation, infection, repair mechanism or in programmed cell death. The role of Atg1 and its regulation is best studied under nutrient starvation and the corresponding arrest of growth.
  A key enzyme in the signalling pathway of nutrient availability is TOR, of which two isoforms exist in yeast(Tor1 and Tor2). These proteins form two distinct complexes, termed TORC1 and TORC2 of which TORC1 is highly sensitive to cellular nutrient conditions. Under nutrient rich conditions, TORC1 is active and phosphorylates Atg13 at multiple sites, thereby inhibiting a complex formation with Atg1. This leads to a decrease in Atg1 kinase activity and decreased autophagy. Upon starvation, Atg13 is rapidly dephosphorylated and forms a complex with Atg1, thereby activating it, which leads to the subsequent assembly of the PAS through recruitment of other Atg proteins.
  In addition to TORC1, protein kinase A (PKA) inhibits autophagy through the phosphorylation of Atg1 and Atg13.
  PKA phosphorylates Atg1 at two distinct serine residues; these modifications were shown to be necessary for Atg1 to properly dissociate from the PAS.
  The downstream substrate of Atg1 kinase hasn't been described yet, and it is still a matter of debate as to whether Atg1 primarily acts on autophagy through its kinase activity or through a structural role during autophagic complex formation. It is possible that the kinase activity of Atg1 is critical to the magnitude of autophagy but not its initiation. At least, large-scale screens led to a candidate list of possible Atg1 substrates, including Atg8 and Atg18. In conclusion, Atg1 first has a structural or scaffolding function during the initial steps of PAS set up, which then is followed by a kinase-dependent phase, that contains protein dynamics at the PAS.
caption: Molecular mechanism of Atg1 complex regulation by phosphorylation of Atg13 through TOR kinase under nutrient rich conditions.
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