Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects
The precise function of <i>CERKL</i>, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that <i>CERKL</i> is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is re...
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MDPI AG
2021-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/12/2018 |
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| author | Rocío García-Arroyo Aleix Gavaldà-Navarro Francesc Villarroya Gemma Marfany Serena Mirra |
| author_facet | Rocío García-Arroyo Aleix Gavaldà-Navarro Francesc Villarroya Gemma Marfany Serena Mirra |
| author_sort | Rocío García-Arroyo |
| collection | DOAJ |
| description | The precise function of <i>CERKL</i>, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that <i>CERKL</i> 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 <i>CERKL</i> 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 <i>CERKL</i> increases the vulnerability of RPE mitochondria, which show a shorter size and altered shape, particularly upon sodium arsenite treatment. <i>CERKL</i>-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 <i>CERKL</i> 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 <i>CERKL</i> mutations. |
| first_indexed | 2024-03-10T04:38:53Z |
| format | Article |
| id | doaj.art-b5a7d3f782e8436cb2f389002b955895 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:53Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b5a7d3f782e8436cb2f389002b9558952023-11-23T03:34:25ZengMDPI AGAntioxidants2076-39212021-12-011012201810.3390/antiox10122018Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress EffectsRocío García-Arroyo0Aleix Gavaldà-Navarro1Francesc Villarroya2Gemma Marfany3Serena Mirra4Department of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, SpainInstitut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, SpainInstitut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, SpainThe precise function of <i>CERKL</i>, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that <i>CERKL</i> 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 <i>CERKL</i> 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 <i>CERKL</i> increases the vulnerability of RPE mitochondria, which show a shorter size and altered shape, particularly upon sodium arsenite treatment. <i>CERKL</i>-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 <i>CERKL</i> 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 <i>CERKL</i> mutations.https://www.mdpi.com/2076-3921/10/12/2018retinitis pigmentosa<i>CERKL</i>retinal pigment epitheliummitochondrial networkoxidative stress |
| spellingShingle | Rocío García-Arroyo Aleix Gavaldà-Navarro Francesc Villarroya Gemma Marfany Serena Mirra Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects Antioxidants retinitis pigmentosa <i>CERKL</i> retinal pigment epithelium mitochondrial network oxidative stress |
| title | Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects |
| title_full | Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects |
| title_fullStr | Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects |
| title_full_unstemmed | Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects |
| title_short | Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects |
| title_sort | overexpression of cerkl protects retinal pigment epithelium mitochondria from oxidative stress effects |
| topic | retinitis pigmentosa <i>CERKL</i> retinal pigment epithelium mitochondrial network oxidative stress |
| url | https://www.mdpi.com/2076-3921/10/12/2018 |
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