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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Bibliographic Details
Authors: 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
Format: article
Status:Versión aceptada para publicación
Publication Date:2021
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/178699
Online Access:https://hdl.handle.net/2445/178699
Access Level:Open access
Keyword:Malalties de la retina
Mitocondris
Mamífers
Retinal diseases
Mitochondria
Mammals
Description
Summary: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.

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