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Decoding the function of Atg13 phosphorylation reveals a role of Atg11 in bulk autophagy initiation

Anuradha Bhattacharya1,2,3, Raffaela Torggler1,2, Wolfgang Reiter4,5

  • 1Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.

EMBO Reports
|January 17, 2024
PubMed

Insights

Dynamic phosphorylation of Atg13 is crucial for regulating autophagy initiation. Disrupting this balance leads to detrimental levels of autophagy, impacting cell survival.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a fundamental cellular process for degrading damaged components.
  • Autophagy initiation involves the assembly of autophagy-related (Atg) proteins at the phagophore assembly site.
  • Atg13 is a key protein in autophagy initiation, characterized by extensive phosphorylation, but the functional role of these sites remains unclear.

Purpose of the Study:

  • To comprehensively analyze the role of phosphorylation events on Atg13 during nutrient-rich conditions and nitrogen starvation.
  • To elucidate how dynamic phosphorylation of Atg13 regulates autophagy initiation and cell survival.

Main Methods:

  • Identification and functional characterization of 48 in vivo phosphorylation sites on Atg13.
  • Generation of reciprocal mutants mimicking dephosphorylated (active) and phosphorylated (inactive) states of Atg13.
  • Investigation of Atg11 involvement in bulk autophagy during nitrogen starvation.

Main Results:

  • Disruption of Atg13 phosphorylation dynamics resulted in insufficient or excessive autophagy, both detrimental to cell survival.
  • 48 in vivo phosphorylation sites on Atg13 were identified and functionally characterized.
  • Atg11 was shown to contribute to bulk autophagy during nitrogen starvation by driving phase separation at the phagophore assembly site.

Conclusions:

  • Post-translational regulation of Atg13 through phosphorylation is critical for controlling autophagy initiation.
  • Dynamic regulation of Atg13 phosphorylation provides layers of control for bulk autophagy activity.
  • These findings highlight the integration of cellular signals through Atg13 phosphorylation.
Keywords:
Atg1 Kinase ComplexAtg11Atg13AutophagyPAS Formation

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