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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Veröffentlicht in: | Neurobiology of disease 2021-08, Vol.156, p.105405-105405, Article 105405 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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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•A pool of CERKL isoforms localize at mitochondria in mouse primary retinal cells.•Cerkl downregulation induces increased autophagy and alterations in mitochondrial network organization in the retina.•Mitochondrial function is impaired in CerklKD/KO retinas impacting mitochondrial-dependent bioenergetics. |
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ISSN: | 0969-9961 1095-953X |
DOI: | 10.1016/j.nbd.2021.105405 |