Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy
Abstract Mitochondria are vital for retinal cell function and survival, and there is growing evidence linking mitochondrial dysfunction to retinal degenerations. Although ARL3 mutations have been linked to multiple forms of retinal degeneration, the relationship between ARL3 and mitochondria remains...
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Wiley
2024-11-01
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| Series: | FASEB BioAdvances |
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| Online Access: | https://doi.org/10.1096/fba.2023-00138 |
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| author | Xiaoli Zhang Shun Yao Lujia Zhang Beisi Zhang Mingzhu Yang Qingge Guo Jin Xu Zhongfeng Wang Bo Lei Xiuxiu Jin |
| author_facet | Xiaoli Zhang Shun Yao Lujia Zhang Beisi Zhang Mingzhu Yang Qingge Guo Jin Xu Zhongfeng Wang Bo Lei Xiuxiu Jin |
| author_sort | Xiaoli Zhang |
| collection | DOAJ |
| description | Abstract Mitochondria are vital for retinal cell function and survival, and there is growing evidence linking mitochondrial dysfunction to retinal degenerations. Although ARL3 mutations have been linked to multiple forms of retinal degeneration, the relationship between ARL3 and mitochondria remains unexplored. Herein, we investigated the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F mutations on mitochondrial function in fibroblasts obtained from patients with ARL3‐related rod‐cone dystrophy. Our findings revealed that these mutations led to a decrease in mitochondrial respiration, an increase in the accumulation mitochondrial reactive oxygen species (ROS), and induction of apoptosis in fibroblasts. Additionally, we conducted a comparative analysis of the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F proteins on mitochondria in ARPE‐19 cells. Results showed that ARL3T31A and ARL3T31A/C118F not only affected mitochondrial function but also induced apoptosis in ARPE‐19 cells. Conversely, ARL3C118F primarily influenced cell apoptosis with minimal effects on mitochondrial function in ARPE‐19 cells. Transcriptome analysis further suggested the involvement of respiratory electron transport, response to ROS, and apoptotic signaling pathways in ARL3T31A/C118F cells. Our study demonstrated that ARL3‐related mutations play a significant role in the diversity of mitochondrial function, providing novel insights into the functional analysis of ARL3‐related mutations. |
| format | Article |
| id | doaj-art-8b89c51d5f1143699d937fb8b3c3cfcd |
| institution | OA Journals |
| issn | 2573-9832 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
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| spelling | doaj-art-8b89c51d5f1143699d937fb8b3c3cfcd2025-08-20T02:12:33ZengWileyFASEB BioAdvances2573-98322024-11-0161155556410.1096/fba.2023-00138Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophyXiaoli Zhang0Shun Yao1Lujia Zhang2Beisi Zhang3Mingzhu Yang4Qingge Guo5Jin Xu6Zhongfeng Wang7Bo Lei8Xiuxiu Jin9Institute of Neuroscience and The Third Affiliated Hospital of Zhengzhou University Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaInstitute of Neuroscience and The Third Affiliated Hospital of Zhengzhou University Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaInstitute of Neuroscience and The Third Affiliated Hospital of Zhengzhou University Zhengzhou ChinaHenan Eye Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital Zhengzhou ChinaInstitute of Neuroscience and The Third Affiliated Hospital of Zhengzhou University Zhengzhou ChinaAbstract Mitochondria are vital for retinal cell function and survival, and there is growing evidence linking mitochondrial dysfunction to retinal degenerations. Although ARL3 mutations have been linked to multiple forms of retinal degeneration, the relationship between ARL3 and mitochondria remains unexplored. Herein, we investigated the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F mutations on mitochondrial function in fibroblasts obtained from patients with ARL3‐related rod‐cone dystrophy. Our findings revealed that these mutations led to a decrease in mitochondrial respiration, an increase in the accumulation mitochondrial reactive oxygen species (ROS), and induction of apoptosis in fibroblasts. Additionally, we conducted a comparative analysis of the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F proteins on mitochondria in ARPE‐19 cells. Results showed that ARL3T31A and ARL3T31A/C118F not only affected mitochondrial function but also induced apoptosis in ARPE‐19 cells. Conversely, ARL3C118F primarily influenced cell apoptosis with minimal effects on mitochondrial function in ARPE‐19 cells. Transcriptome analysis further suggested the involvement of respiratory electron transport, response to ROS, and apoptotic signaling pathways in ARL3T31A/C118F cells. Our study demonstrated that ARL3‐related mutations play a significant role in the diversity of mitochondrial function, providing novel insights into the functional analysis of ARL3‐related mutations.https://doi.org/10.1096/fba.2023-00138apoptosisARL3mitochondriamutationrod‐cone dystrophy |
| spellingShingle | Xiaoli Zhang Shun Yao Lujia Zhang Beisi Zhang Mingzhu Yang Qingge Guo Jin Xu Zhongfeng Wang Bo Lei Xiuxiu Jin Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy FASEB BioAdvances apoptosis ARL3 mitochondria mutation rod‐cone dystrophy |
| title | Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy |
| title_full | Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy |
| title_fullStr | Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy |
| title_full_unstemmed | Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy |
| title_short | Mitochondrial functional impairment in ARL3‐mutation related rod‐cone dystrophy |
| title_sort | mitochondrial functional impairment in arl3 mutation related rod cone dystrophy |
| topic | apoptosis ARL3 mitochondria mutation rod‐cone dystrophy |
| url | https://doi.org/10.1096/fba.2023-00138 |
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