Related Experiment Video

Updated: Sep 9, 2025

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

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Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts

Tak Shun Fung1, Amrapali Ghosh2, Maite R Zavala2

  • 1Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

EMBO Reports
|August 29, 2025
PubMed

Insights

Acute Damage-induced Actin (ADA) delays mitophagy after mitochondrial damage. Inhibiting ADA accelerates Parkin recruitment and restores mitophagy during chronic damage by disrupting ER-mitochondria contacts.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Cellular Homeostasis

Background:

  • Mitochondrial damage triggers cellular responses for homeostasis.
  • Rapid actin polymerization (ADA) occurs within minutes of mitochondrial damage.
  • ADA facilitates metabolic shifts during mitochondrial dysfunction.

Purpose of the Study:

  • To investigate the role of ADA in Pink1/Parkin mediated mitochondrial quality control.
  • To elucidate the mechanism by which ADA affects Parkin recruitment.
  • To understand ADA's impact on mitophagy during acute and chronic mitochondrial damage.

Main Methods:

  • Investigated ADA's effect on Parkin recruitment to damaged mitochondria.
  • Examined the role of Arp2/3 complex in ADA-mediated disruption of ER-mitochondria contacts.
  • Assessed the impact of ER-mitochondria tethers on Parkin and LC3 recruitment.
  • Studied the effect of ADA inhibition on mitophagy during chronic mitochondrial dysfunction.

Main Results:

  • Inhibiting ADA accelerates Parkin recruitment to depolarized mitochondria.
  • ADA disrupts ER-mitochondria contacts via Arp2/3 complex, hindering Parkin recruitment.
  • Overexpressing ER-mitochondria tethers overrides ADA's effect, promoting Parkin and LC3 recruitment.
  • ADA blocks Parkin and LC3 recruitment during chronic damage, which is reversible upon ADA inhibition.

Conclusions:

  • ADA delays mitophagy following acute mitochondrial damage.
  • ADA acts as a protective mechanism by blocking mitophagy during chronic mitochondrial damage.
  • ADA's regulation of ER-mitochondria contacts is crucial for controlling mitophagy.
Keywords:
ActinArp2/3 ComplexERLC3Parkin

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