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Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects

The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is resilient against oxidative stress in th...

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Autores principales: García-Arroyo, Rocío, Gavaldà-Navarro, Aleix, Villarroya, Francesc, Marfany, Gemma, Mirra, Serena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698444/
https://www.ncbi.nlm.nih.gov/pubmed/34943121
http://dx.doi.org/10.3390/antiox10122018
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author García-Arroyo, Rocío
Gavaldà-Navarro, Aleix
Villarroya, Francesc
Marfany, Gemma
Mirra, Serena
author_facet García-Arroyo, Rocío
Gavaldà-Navarro, Aleix
Villarroya, Francesc
Marfany, Gemma
Mirra, Serena
author_sort García-Arroyo, Rocío
collection PubMed
description The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is resilient against oxidative stress in the retina. Mutations in most RP genes affect photoreceptors, but retinal pigment epithelium (RPE) cells may be also altered. Here, we aimed to analyze the effect of CERKL overexpression and depletion in vivo and in vitro, focusing on the state of the mitochondrial network under oxidative stress conditions. Our work indicates that the depletion of CERKL increases the vulnerability of RPE mitochondria, which show a shorter size and altered shape, particularly upon sodium arsenite treatment. CERKL-depleted cells have dysfunctional mitochondrial respiration particularly upon oxidative stress conditions. The overexpression of two human CERKL isoforms (558 aa and 419 aa), which display different protein domains, shows that a pool of CERKL localizes at mitochondria in RPE cells and that CERKL protects the mitochondrial network—both in size and shape—against oxidative stress. Our results support CERKL being a resilient gene that regulates the mitochondrial network in RPE as in retinal neurons and suggest that RPE cell alteration contributes to particular phenotypic traits in patients carrying CERKL mutations.
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spelling pubmed-86984442021-12-24 Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects García-Arroyo, Rocío Gavaldà-Navarro, Aleix Villarroya, Francesc Marfany, Gemma Mirra, Serena Antioxidants (Basel) Article The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is resilient against oxidative stress in the retina. Mutations in most RP genes affect photoreceptors, but retinal pigment epithelium (RPE) cells may be also altered. Here, we aimed to analyze the effect of CERKL overexpression and depletion in vivo and in vitro, focusing on the state of the mitochondrial network under oxidative stress conditions. Our work indicates that the depletion of CERKL increases the vulnerability of RPE mitochondria, which show a shorter size and altered shape, particularly upon sodium arsenite treatment. CERKL-depleted cells have dysfunctional mitochondrial respiration particularly upon oxidative stress conditions. The overexpression of two human CERKL isoforms (558 aa and 419 aa), which display different protein domains, shows that a pool of CERKL localizes at mitochondria in RPE cells and that CERKL protects the mitochondrial network—both in size and shape—against oxidative stress. Our results support CERKL being a resilient gene that regulates the mitochondrial network in RPE as in retinal neurons and suggest that RPE cell alteration contributes to particular phenotypic traits in patients carrying CERKL mutations. MDPI 2021-12-19 /pmc/articles/PMC8698444/ /pubmed/34943121 http://dx.doi.org/10.3390/antiox10122018 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
García-Arroyo, Rocío
Gavaldà-Navarro, Aleix
Villarroya, Francesc
Marfany, Gemma
Mirra, Serena
Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title_full Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title_fullStr Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title_full_unstemmed Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title_short Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
title_sort overexpression of cerkl protects retinal pigment epithelium mitochondria from oxidative stress effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698444/
https://www.ncbi.nlm.nih.gov/pubmed/34943121
http://dx.doi.org/10.3390/antiox10122018
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