CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina

The retina is a highly active metabolic organ that displays a particular vulnerability to genetic and environmental factors causing stress and homeostatic imbalance. Mitochondria constitute a bioenergetic hub that coordinates stress response and cellular homeostasis, therefore structural and functio...

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Autores: Mirra, Serena, García-Arroyo, Rocío, Domènech, Elena B., Gavaldà i Navarro, Aleix, Herrera Úbeda, Carlos, Oliva, Clara, Garcia Fernández, Jordi, Artuch Iriberri, Rafael, Villarroya i Gombau, Francesc, Marfany i Nadal, Gemma
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/178699
Acceso en línea:https://hdl.handle.net/2445/178699
Access Level:acceso abierto
Palabra clave:Malalties de la retina
Mitocondris
Mamífers
Retinal diseases
Mitochondria
Mammals
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spelling CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retinaMirra, SerenaGarcía-Arroyo, RocíoDomènech, Elena B.Gavaldà i Navarro, AleixHerrera Úbeda, CarlosOliva, ClaraGarcia Fernández, JordiArtuch Iriberri, RafaelVillarroya i Gombau, FrancescMarfany i Nadal, GemmaMalalties de la retinaMitocondrisMamífersRetinal diseasesMitochondriaMammalsThe retina is a highly active metabolic organ that displays a particular vulnerability to genetic and environmental factors causing stress and homeostatic imbalance. Mitochondria constitute a bioenergetic hub that coordinates stress response and cellular homeostasis, therefore structural and functional regulation of the mitochondrial dynamic network is essential for the mammalian retina. CERKL (ceramide kinase like) is a retinal degeneration gene whose mutations cause Retinitis Pigmentosa in humans, a visual disorder characterized by photoreceptors neurodegeneration and progressive vision loss. CERKL produces multiple isoforms with a dynamic subcellular localization. Here we show that a pool of CERKL isoforms localizes at mitochondria in mouse retinal ganglion cells. The depletion of CERKL levels in CerklKD/KO (knockdown/knockout) mouse retinas cause increase of autophagy, mitochondrial fragmentation, alteration of mitochondrial distribution, and dysfunction of mitochondrial-dependent bioenergetics and metabolism. Our results support CERKL as a regulator of autophagy and mitochondrial biology in the mammalian retina.Elsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/178699Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.nbd.2021.105405Neurobiology of Disease, 2021, vol. 156, p. 105405https://doi.org/10.1016/j.nbd.2021.105405cc-by-nc-nd (c) Elsevier, 2021https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1786992026-05-27T06:46:51Z
dc.title.none.fl_str_mv CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
title CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
spellingShingle CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
Mirra, Serena
Malalties de la retina
Mitocondris
Mamífers
Retinal diseases
Mitochondria
Mammals
title_short CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
title_full CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
title_fullStr CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
title_full_unstemmed CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
title_sort CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
dc.creator.none.fl_str_mv Mirra, Serena
García-Arroyo, Rocío
Domènech, Elena B.
Gavaldà i Navarro, Aleix
Herrera Úbeda, Carlos
Oliva, Clara
Garcia Fernández, Jordi
Artuch Iriberri, Rafael
Villarroya i Gombau, Francesc
Marfany i Nadal, Gemma
author Mirra, Serena
author_facet Mirra, Serena
García-Arroyo, Rocío
Domènech, Elena B.
Gavaldà i Navarro, Aleix
Herrera Úbeda, Carlos
Oliva, Clara
Garcia Fernández, Jordi
Artuch Iriberri, Rafael
Villarroya i Gombau, Francesc
Marfany i Nadal, Gemma
author_role author
author2 García-Arroyo, Rocío
Domènech, Elena B.
Gavaldà i Navarro, Aleix
Herrera Úbeda, Carlos
Oliva, Clara
Garcia Fernández, Jordi
Artuch Iriberri, Rafael
Villarroya i Gombau, Francesc
Marfany i Nadal, Gemma
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties de la retina
Mitocondris
Mamífers
Retinal diseases
Mitochondria
Mammals
topic Malalties de la retina
Mitocondris
Mamífers
Retinal diseases
Mitochondria
Mammals
description The retina is a highly active metabolic organ that displays a particular vulnerability to genetic and environmental factors causing stress and homeostatic imbalance. Mitochondria constitute a bioenergetic hub that coordinates stress response and cellular homeostasis, therefore structural and functional regulation of the mitochondrial dynamic network is essential for the mammalian retina. CERKL (ceramide kinase like) is a retinal degeneration gene whose mutations cause Retinitis Pigmentosa in humans, a visual disorder characterized by photoreceptors neurodegeneration and progressive vision loss. CERKL produces multiple isoforms with a dynamic subcellular localization. Here we show that a pool of CERKL isoforms localizes at mitochondria in mouse retinal ganglion cells. The depletion of CERKL levels in CerklKD/KO (knockdown/knockout) mouse retinas cause increase of autophagy, mitochondrial fragmentation, alteration of mitochondrial distribution, and dysfunction of mitochondrial-dependent bioenergetics and metabolism. Our results support CERKL as a regulator of autophagy and mitochondrial biology in the mammalian retina.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/178699
url https://hdl.handle.net/2445/178699
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.nbd.2021.105405
Neurobiology of Disease, 2021, vol. 156, p. 105405
https://doi.org/10.1016/j.nbd.2021.105405
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier, 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier, 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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