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Updated: Jun 14, 2025
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
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The ULK1 effector BAG2 regulates autophagy initiation by modulating AMBRA1 localization.
Devanarayanan Siva Sankar1, Stephanie Kaeser-Pebernard1, Christine Vionnet1
1Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
Cell Reports
|August 29, 2024
Summary
Autophagy initiation involves the ULK1 complex interacting with kinases and autophagy receptors. ULK1 phosphorylates BAG2 under starvation, promoting autophagy by regulating AMBRA1 localization.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Autophagy is a fundamental cellular process for degrading damaged components.
- The ULK1 complex is a key initiator of autophagy.
- Understanding the ULK1 complex's regulation and interactions is crucial for deciphering autophagy pathways.
Purpose of the Study:
- To comprehensively map the ULK1 complex interactome.
- To investigate the role of ULK1 complex interactions in response to nutrient starvation.
- To elucidate the regulatory mechanism of autophagy initiation involving BAG2 and AMBRA1.
Main Methods:
- Affinity purification-mass spectrometry
- Proximity labeling-mass spectrometry
- Analysis of protein-protein interactions
- Phosphorylation site mapping
Main Results:
- A deep interactome of the ULK1 complex (ULK1, ATG13, ATG101, RB1CC1/FIP200) was generated.
- The ULK1 complex interacts with kinases, phosphatases, and selective autophagy receptors under starvation.
- ULK1-mediated phosphorylation of BAG2 on Ser31 under starvation promotes AMBRA1 recruitment to the ER, enhancing autophagy.
Conclusions:
- The ULK1 complex forms a signalosome that integrates starvation signals.
- Nutrient starvation activates selective autophagy pathways via ULK1 complex interactions.
- BAG2 acts as a nutritional sensor, with its phosphorylation state by ULK1 dynamically regulating autophagy induction.
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