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Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
Published on: June 30, 2023
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ATPase activity of DFCP1 controls selective autophagy
Viola Nähse1,2,3, Camilla Raiborg4,5, Kia Wee Tan4,5,6
1Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway. Viola.Naehse@rr-research.no.
Nature Communications
|July 8, 2023
Summary
DFCP1 is an ATPase essential for selective autophagy. It constricts omegasomes to release autophagosomes, ensuring cellular homeostasis by removing damaged components via pathways like aggrephagy and mitophagy.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Cellular homeostasis relies on selective autophagy, removing damaged organelles and protein aggregates.
- p62/SQSTM1 acts as a cargo adaptor in selective autophagy.
- Omegasomes, ER-derived structures, are sites of autophagosome formation, marked by DFCP1.
Purpose of the Study:
- To elucidate the function of DFCP1 in omegasome formation and constriction.
- To investigate the role of DFCP1's ATPase activity in selective autophagy.
- To understand how DFCP1 regulates autophagosome release for cellular quality control.
Main Methods:
- Investigated DFCP1's ATPase activity through biochemical assays.
- Utilized gene depletion and knockout strategies to assess DFCP1's role in autophagy.
- Examined omegasome formation, constriction, and autophagosome release using microscopy.
Main Results:
- DFCP1 functions as a membrane-binding, ATP-dependent dimerizing ATPase.
- DFCP1 is crucial for p62 autophagic flux, independent of bulk autophagy levels.
- DFCP1 deficiency impairs omegasome constriction and delays autophagosome release, inhibiting selective autophagy pathways.
Conclusions:
- DFCP1's ATPase activity drives omegasome constriction, facilitating autophagosome release.
- DFCP1 is essential for selective autophagy, including aggrephagy, mitophagy, and micronucleophagy.
- DFCP1 plays a critical role in maintaining cellular homeostasis through regulated autophagosome formation and cargo removal.
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