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Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
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BNIP3L/NIX regulates both mitophagy and pexophagy
Léa P Wilhelm1, Juan Zapata-Muñoz2, Beatriz Villarejo-Zori2
1MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
The EMBO Journal
|October 10, 2022
Summary
The protein BNIP3L/NIX coordinates the breakdown of both mitochondria (mitophagy) and peroxisomes (pexophagy) via selective autophagy. This dual role highlights the interconnectedness of these essential cellular recycling pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Mitochondria and peroxisomes are metabolically related organelles with crucial cellular functions.
- Both organelles can be degraded via selective autophagy, known as mitophagy and pexophagy, respectively.
- The coordination and conditions triggering simultaneous mitophagy and pexophagy remain largely unknown.
Purpose of the Study:
- To investigate if mitophagy and pexophagy are activated under similar conditions.
- To elucidate the molecular mechanisms coordinating these selective autophagy pathways.
- To determine the role of BNIP3L/NIX in pexophagy.
Main Methods:
- Utilized iron chelation to induce selective autophagy.
- Investigated the role of BNIP3L/NIX in mitophagy and pexophagy.
- Examined mouse tissue lacking NIX for peroxisomal content.
- Observed mitophagy and pexophagy during cardiomyocyte and erythrocyte differentiation.
Main Results:
- Multiple selective autophagy pathways, including mitophagy and pexophagy, are activated by iron chelation.
- BNIP3L/NIX, a known mitophagy receptor, was found to localize to peroxisomes and drive pexophagy.
- Mice lacking NIX exhibited increased peroxisomal content, confirming NIX's role in pexophagy in vivo.
- Pexophagy is upregulated under the same physiological conditions that induce mitophagy.
Conclusions:
- BNIP3L/NIX plays a dual role, mediating both mitophagy and pexophagy.
- This discovery reveals a molecular link between mitochondrial and peroxisomal turnover.
- The findings illustrate the interconnectedness of selective autophagy pathways in cellular homeostasis.
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