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Updated: Jun 7, 2025
09:29
Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
Published on: May 4, 2016
7.2K
Opposing roles for AMPK in regulating distinct mitophagy pathways.
Marianna Longo1, Aniketh Bishnu1, Pierpaolo Risiglione1
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Molecular Cell
|November 12, 2024
Summary
AMP-activated protein kinase (AMPK) regulates mitophagy. AMPK activation inhibits programmed mitophagy of functional mitochondria while promoting mitophagy of damaged ones.
Area of Science:
- Cellular Biology
- Mitochondrial Dynamics
- Autophagy
Background:
- Mitophagy, the selective degradation of mitochondria, typically targets damaged organelles.
- However, functional mitochondria can also undergo mitophagy, a process termed programmed mitophagy, involving receptors like NIX and BNIP3.
- The role of AMP-activated protein kinase (AMPK) in programmed mitophagy remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of AMPK in programmed mitophagy.
- To elucidate the molecular mechanisms by which AMPK influences mitophagy of both functional and damaged mitochondria.
Main Methods:
- Utilized cell culture and the mito-QC mouse model for in vivo studies.
- Investigated mitophagy pathways, including NIX-dependent and depolarization-induced mitophagy.
- Analyzed protein phosphorylation events, specifically focusing on ULK1 and Parkin.
Main Results:
- AMPK directly inhibits NIX-dependent programmed mitophagy by phosphorylating ULK1 at Ser556 and Ser694, leading to 14-3-3-mediated sequestration.
- AMPK activation enhances depolarization-induced mitophagy of damaged mitochondria by increasing Parkin phosphorylation, independent of ULK1.
- These findings were validated in both cultured cells and in vivo mouse models.
Conclusions:
- AMPK activation differentially regulates mitophagy pathways.
- AMPK downregulates the mitophagy of functional mitochondria through ULK1 inhibition.
- AMPK enhances the mitophagy of damaged mitochondria via Parkin activation.
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