Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects.
Por:
García-Arroyo R, Gavaldà-Navarro A, Villarroya-Gombau F, Marfany G and Mirra S
Publicada:
19 dic 2021
Ahead of Print:
19 dic 2021
Resumen:
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.
Filiaciones:
García-Arroyo R:
Department of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
Gavaldà-Navarro A:
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
Department of Biochemistry and Molecular Biomedicine, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain
CIBEROBN, Instituto de Salud Carlos III, 28029 Madrid, Spain
Villarroya-Gombau F:
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
Department of Biochemistry and Molecular Biomedicine, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain
CIBEROBN, Instituto de Salud Carlos III, 28029 Madrid, Spain
Marfany G:
Department of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
DBGen Ocular Genomics, 08028 Barcelona, Spain
Mirra S:
Department of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
Open Access
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