A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis
Abstract Autosomal dominant optic atrophy (ADOA) is a dominantly inherited optic neuropathy, affecting the specific loss of retinal ganglion cells (RGCs). The majority of affected cases of ADOA are associated with mutations in OPA1 gene. Our previous investigation identified the c.1198C > G (p.P4...
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2017
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oai:doaj.org-article:fcfbc8471f944ec8a3d919a33f79392d2021-12-02T11:40:30ZA novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis10.1038/s41598-017-05571-y2045-2322https://doaj.org/article/fcfbc8471f944ec8a3d919a33f79392d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05571-yhttps://doaj.org/toc/2045-2322Abstract Autosomal dominant optic atrophy (ADOA) is a dominantly inherited optic neuropathy, affecting the specific loss of retinal ganglion cells (RGCs). The majority of affected cases of ADOA are associated with mutations in OPA1 gene. Our previous investigation identified the c.1198C > G (p.P400A) mutation in the OPA1 in a large Han Chinese family with ADOA. In this report, we performed a functional characterization using lymphoblostoid cell lines derived from affected members of this family and control subjects. Mutant cell lines exhibited the aberrant mitochondrial morphology. A ~24.6% decrease in the mitochondrial DNA (mtDNA) copy number was observed in mutant cell lines, as compared with controls. Western blotting analysis revealed the variable reductions (~45.7%) in four mtDNA-encoded polypeptides in mutant cell lines. The impaired mitochondrial translation caused defects in respiratory capacity. Furthermore, defects in mitochondrial ATP synthesis and mitochondrial membrane potential (ΔΨm) were observed in mutant cell lines. These abnormalities resulted in the accumulation of oxidative damage and increasing of apoptosis in the mutant cell lines, as compared with controls. All those alterations may cause the primary degeneration of RGCs and subsequent visual loss. These data provided the direct evidence for c.1198C > G mutation leading to ADOA. Our findings may provide new insights into the understanding of pathophysiology of ADOA.Juanjuan ZhangXiaoling LiuXiaoyang LiangYuanyuan LuLing ZhuRuning FuYanchun JiWenlu FanJie ChenBing LinYimin YuanPingping JiangXiangtian ZhouMin-Xin GuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Juanjuan Zhang Xiaoling Liu Xiaoyang Liang Yuanyuan Lu Ling Zhu Runing Fu Yanchun Ji Wenlu Fan Jie Chen Bing Lin Yimin Yuan Pingping Jiang Xiangtian Zhou Min-Xin Guan A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| description |
Abstract Autosomal dominant optic atrophy (ADOA) is a dominantly inherited optic neuropathy, affecting the specific loss of retinal ganglion cells (RGCs). The majority of affected cases of ADOA are associated with mutations in OPA1 gene. Our previous investigation identified the c.1198C > G (p.P400A) mutation in the OPA1 in a large Han Chinese family with ADOA. In this report, we performed a functional characterization using lymphoblostoid cell lines derived from affected members of this family and control subjects. Mutant cell lines exhibited the aberrant mitochondrial morphology. A ~24.6% decrease in the mitochondrial DNA (mtDNA) copy number was observed in mutant cell lines, as compared with controls. Western blotting analysis revealed the variable reductions (~45.7%) in four mtDNA-encoded polypeptides in mutant cell lines. The impaired mitochondrial translation caused defects in respiratory capacity. Furthermore, defects in mitochondrial ATP synthesis and mitochondrial membrane potential (ΔΨm) were observed in mutant cell lines. These abnormalities resulted in the accumulation of oxidative damage and increasing of apoptosis in the mutant cell lines, as compared with controls. All those alterations may cause the primary degeneration of RGCs and subsequent visual loss. These data provided the direct evidence for c.1198C > G mutation leading to ADOA. Our findings may provide new insights into the understanding of pathophysiology of ADOA. |
| format |
article |
| author |
Juanjuan Zhang Xiaoling Liu Xiaoyang Liang Yuanyuan Lu Ling Zhu Runing Fu Yanchun Ji Wenlu Fan Jie Chen Bing Lin Yimin Yuan Pingping Jiang Xiangtian Zhou Min-Xin Guan |
| author_facet |
Juanjuan Zhang Xiaoling Liu Xiaoyang Liang Yuanyuan Lu Ling Zhu Runing Fu Yanchun Ji Wenlu Fan Jie Chen Bing Lin Yimin Yuan Pingping Jiang Xiangtian Zhou Min-Xin Guan |
| author_sort |
Juanjuan Zhang |
| title |
A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| title_short |
A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| title_full |
A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| title_fullStr |
A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| title_full_unstemmed |
A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis |
| title_sort |
novel adoa-associated opa1 mutation alters the mitochondrial function, membrane potential, ros production and apoptosis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/fcfbc8471f944ec8a3d919a33f79392d |
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