CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina
Por:
Mirra S, Arroyo RG, Domènech EB, Gavaldà-Navarro A, Herrera-Úbeda C, Oliva C, Garcia-Fernàndez J, Artuch-Iriberri R, Villarroya-Gombau F and Marfany G
Publicada:
1 ago 2021
Ahead of Print:
1 may 2021
Categoría:
Neurology
Resumen:
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 mitochondrialdependent bioenergetics and metabolism. Our results support CERKL as a regulator of autophagy and mitochondrial biology in the mammalian retina.
Filiaciones:
Mirra S:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Institut de Biomedicina de la Universitat de Barcelona- Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain
Arroyo RG:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Domènech EB:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Gavaldà-Navarro A:
Institut de Biomedicina de la Universitat de Barcelona- Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain
CIBEROBN, Instituto de Salud Carlos III, Spain
Herrera-Úbeda C:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Oliva C:
Clinical Biochemistry Department, Hospital Sant Joan de Déu, Spain
Garcia-Fernàndez J:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Artuch-Iriberri R:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Clinical Biochemistry Department, Hospital Sant Joan de Déu, Spain
Villarroya-Gombau F:
Institut de Biomedicina de la Universitat de Barcelona- Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain
Department of Biochemistry and Molecular Biomedicine, Barcelona, Spain
CIBEROBN, Instituto de Salud Carlos III, Spain
Marfany G:
Department of Genetics, Microbiology and Statistics and Institute of Biomedicine (IBUB), Faculty of Biology, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Institut de Biomedicina de la Universitat de Barcelona- Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain
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