The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy

Juan Zapata-Muñoz; Juan Ignacio Jiménez-Loygorri; Michael Stumpe; Beatriz Villarejo-Zori; Sandra Alonso-Gil; Petra Terešak; Benan J. Mathai; Ian G. Ganley; Anne Simonsen; Jörn Dengjel; Patricia Boya

doi:10.1016/j.jmb.2025.169263

The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy

Juan Zapata-Muñoz
, Juan Ignacio Jiménez-Loygorri
, Michael Stumpe
, Beatriz Villarejo-Zori
, Sandra Alonso-Gil
, Petra Terešak
, Benan J. Mathai
, Ian G. Ganley
, Anne Simonsen
, Jörn Dengjel
, Patricia Boya (Lead / Corresponding author)

MRC PPU

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

102 Downloads (Pure)

Abstract

Mitophagy, the selective degradation of mitochondria, is essential for retinal ganglion cell (RGC) differentiation and retinal homeostasis. However, the specific mitophagy pathways involved and their temporal dynamics during retinal development and maturation remain poorly understood. Using proteomics analysis of isolated mouse retinas across developmental stages and the mitophagy reporter mouse line, mito-QC, we characterized mitophagy throughout retinogenesis. While mitolysosomes were more prevalent in the mature retina, we observed two distinct mitophagy peaks during embryonic development. The first, independent of PTEN-induced kinase 1 (PINK1) activation, was associated with RGCs. The second, PINK1-dependent peak was triggered after an increase in retinal oxidative stress. This PINK1-dependent, oxidative stress-induced mitophagy pathway is conserved in mice and zebrafish, providing the first evidence of programmed, PINK1-dependent mitophagy during development.

Original language	English
Article number	169263
Number of pages	15
Journal	Journal of Molecular Biology
Volume	437
Issue number	18
Early online date	3 Jun 2025
DOIs	https://doi.org/10.1016/j.jmb.2025.169263
Publication status	Published - 15 Sept 2025

Keywords

autophagy
development
mitophagy
PINK1
retina

ASJC Scopus subject areas

Biophysics
Structural Biology
Molecular Biology

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10.1016/j.jmb.2025.169263Licence: CC BY

Final published versionFinal published version, 5.64 MBLicence: CC BY

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Zapata-Muñoz, J., Jiménez-Loygorri, J. I., Stumpe, M., Villarejo-Zori, B., Alonso-Gil, S., Terešak, P., Mathai, B. J., Ganley, I. G., Simonsen, A., Dengjel, J., & Boya, P. (2025). The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy. Journal of Molecular Biology, 437(18), Article 169263. https://doi.org/10.1016/j.jmb.2025.169263

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title = "The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy",

abstract = "Mitophagy, the selective degradation of mitochondria, is essential for retinal ganglion cell (RGC) differentiation and retinal homeostasis. However, the specific mitophagy pathways involved and their temporal dynamics during retinal development and maturation remain poorly understood. Using proteomics analysis of isolated mouse retinas across developmental stages and the mitophagy reporter mouse line, mito-QC, we characterized mitophagy throughout retinogenesis. While mitolysosomes were more prevalent in the mature retina, we observed two distinct mitophagy peaks during embryonic development. The first, independent of PTEN-induced kinase 1 (PINK1) activation, was associated with RGCs. The second, PINK1-dependent peak was triggered after an increase in retinal oxidative stress. This PINK1-dependent, oxidative stress-induced mitophagy pathway is conserved in mice and zebrafish, providing the first evidence of programmed, PINK1-dependent mitophagy during development.",

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author = "Juan Zapata-Mu{\~n}oz and Jim{\'e}nez-Loygorri, \{Juan Ignacio\} and Michael Stumpe and Beatriz Villarejo-Zori and Sandra Alonso-Gil and Petra Tere{\v s}ak and Mathai, \{Benan J.\} and Ganley, \{Ian G.\} and Anne Simonsen and J{\"o}rn Dengjel and Patricia Boya",

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doi = "10.1016/j.jmb.2025.169263",

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AU - Villarejo-Zori, Beatriz

AU - Alonso-Gil, Sandra

AU - Terešak, Petra

AU - Mathai, Benan J.

AU - Ganley, Ian G.

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AU - Dengjel, Jörn

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AB - Mitophagy, the selective degradation of mitochondria, is essential for retinal ganglion cell (RGC) differentiation and retinal homeostasis. However, the specific mitophagy pathways involved and their temporal dynamics during retinal development and maturation remain poorly understood. Using proteomics analysis of isolated mouse retinas across developmental stages and the mitophagy reporter mouse line, mito-QC, we characterized mitophagy throughout retinogenesis. While mitolysosomes were more prevalent in the mature retina, we observed two distinct mitophagy peaks during embryonic development. The first, independent of PTEN-induced kinase 1 (PINK1) activation, was associated with RGCs. The second, PINK1-dependent peak was triggered after an increase in retinal oxidative stress. This PINK1-dependent, oxidative stress-induced mitophagy pathway is conserved in mice and zebrafish, providing the first evidence of programmed, PINK1-dependent mitophagy during development.

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The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy

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Keywords

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