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Activating Autophagy by Aerobic Exercise in Mice
Published on: February 3, 2017
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The ULK1-FBXW5-SEC23B nexus controls autophagy
Yeon-Tae Jeong1,2, Daniele Simoneschi1,2, Sarah Keegan1,2,3
1Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, United States.
Elife
|January 1, 2019
Summary
The F-box protein FBXW5 targets SEC23B for degradation, limiting autophagy when nutrients are present. Starvation triggers ULK1 to stabilize SEC23B, promoting autophagosome formation and efficient autophagy.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Autophagy is crucial for cellular homeostasis, involving autophagosome formation.
- Coat Protein Complex II (COPII) facilitates autophagosome biogenesis by providing membranes and stimulating LC3 lipidation.
Purpose of the Study:
- To investigate the role of FBXW5 and SEC23B in regulating autophagic flux.
- To elucidate the mechanism by which nutrient availability controls autophagosome biogenesis.
Main Methods:
- Proteasomal degradation assays
- Immunoprecipitation to study protein interactions
- Phosphorylation site analysis (Serine 186)
- Subcellular localization studies (ER-Golgi intermediate compartment)
Main Results:
- FBXW5 targets SEC23B, a COPII component, for proteasomal degradation, limiting autophagic flux under nutrient-rich conditions.
- ULK1-mediated phosphorylation of SEC23B at Serine 186 inhibits FBXW5 binding and subsequent degradation.
- Stabilized SEC23B interacts with SEC24A/B and re-localizes to the ER-Golgi intermediate compartment, enhancing autophagic flux.
Conclusions:
- FBXW5 acts as a negative regulator of COPII-mediated autophagosome biogenesis in the presence of nutrients.
- ULK1-dependent stabilization of SEC23B is a key mechanism for promoting autophagic flux during nutrient starvation.
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