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Related Experiment Video

Updated: Jul 16, 2025

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

ATPase-regulated autophagosome biogenesis.

Viola Nähse^1,2,3, Kay O Schink^1,4, Harald Stenmark^1,2

¹Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, montebello, Oslo Norway.

|September 18, 2023

Summary

ZFYVE1 protein

Keywords:

Aggrephagy Atpase autophagosome micronucleophagy mitophagy omegasome

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Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond

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Area of Science:

Cell Biology
Molecular Biology

Background:

Omegasomes, endoplasmic reticulum structures, are implicated in autophagosome biogenesis.
The precise function of ZFYVE1/DFCP1 in omegasomes and autophagy remains unclear.
ZFYVE1 depletion does not impede bulk autophagy, posing a paradox.

Purpose of the Study:

To investigate the role of ZFYVE1's ATPase domain in omegasome function and autophagy.
To elucidate the mechanism by which ZFYVE1 regulates omegasome constriction and autophagosome completion.

Main Methods:

Site-directed mutagenesis of ZFYVE1's ATPase domain.
Analysis of omegasome morphology, expansion, and maturation.
Assessment of bulk and selective autophagy in ZFYVE1 knockout/mutant cells.

Main Results:

ZFYVE1 dimerization is regulated by ATP binding and hydrolysis.
Mutations affecting ATP binding/hydrolysis inhibit omegasome constriction but not expansion.
Selective autophagy pathways (mitophagy, aggregate clearance) are impaired in ZFYVE1 mutants, unlike bulk autophagy.

Conclusions:

ZFYVE1's ATPase activity is crucial for omegasome constriction and autophagosome completion.
ATP-dependent ZFYVE1 conformational changes likely provide energy for omegasome dynamics.
ZFYVE1 regulates selective autophagy, highlighting its specific role beyond bulk autophagy.