PEX14 powers OPTN (optineurin) to drive peroxisome turnover

Cells maintain organelle integrity and metabolic balance through tightly coordinated quality control systems. Autophagy plays a central role by recycling damaged and unnecessary cellular components, with selective pathways providing specificity through dedicated receptors. Although OPTN is well-established as a receptor for mitophagy, aggrephagy, and xenophagy, its role in pexophagy, the selective autophagic degradation of peroxisomes, has only recently been recognized. Our recent work identifies the peroxisomal membrane protein PEX14 as a critical docking platform for OPTN, enabling recruitment of autophagic machinery and initiation of pexophagy. How PEX14 engages OPTN, what triggers this interaction, and how it drives the autophagic engulfment of peroxisomes remain unclear. In this punctum, we contextualize our findings and highlight unresolved questions that must be addressed to understand the physiological and pathological relevance of this process.

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Publication Details

Journal
Autophagy
Published
2025-12-31
DOI
https://doi.org/10.1080/15548627.2025.2610452
Primary Topic
Autophagy in Disease and Therapy
Type
article
Field-Weighted Citation Impact
0.00
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article

PEX14 powers OPTN (optineurin) to drive peroxisome turnover

Marc Fransen, H T Li, Jorge E. Azevedo
Autophagy
Autophagy in Disease and Therapy
article

PEX14 powers OPTN (optineurin) to drive peroxisome turnover

Marc Fransen, H T Li, Jorge E. Azevedo
article en

Abstract

Cells maintain organelle integrity and metabolic balance through tightly coordinated quality control systems. Autophagy plays a central role by recycling damaged and unnecessary cellular components, with selective pathways providing specificity through dedicated receptors. Although OPTN is well-established as a receptor for mitophagy, aggrephagy, and xenophagy, its role in pexophagy, the selective autophagic degradation of peroxisomes, has only recently been recognized. Our recent work identifies the peroxisomal membrane protein PEX14 as a critical docking platform for OPTN, enabling recruitment of autophagic machinery and initiation of pexophagy. How PEX14 engages OPTN, what triggers this interaction, and how it drives the autophagic engulfment of peroxisomes remain unclear. In this punctum, we contextualize our findings and highlight unresolved questions that must be addressed to understand the physiological and pathological relevance of this process.

AutophagyVol. 22(3)
Universitat Jaume I (ES), Universidade do Porto (PT), University of Toronto (CA)
Openalex Percentile: Top 29%
Autophagy in Disease and Therapy
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