与 ARL3 基因突变相关的视杆细胞色素营养不良症中的线粒体功能障碍

IF 2.5 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaoli Zhang, Shun Yao, Lujia Zhang, Beisi Zhang, Mingzhu Yang, Qingge Guo, Jin Xu, Zhongfeng Wang, Bo Lei, Xiuxiu Jin
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引用次数: 0

摘要

线粒体对视网膜细胞的功能和存活至关重要,越来越多的证据表明线粒体功能障碍与视网膜变性有关。虽然 ARL3 突变与多种形式的视网膜变性有关,但 ARL3 与线粒体之间的关系仍未得到探讨。在此,我们研究了 ARL3T31A、ARL3C118F 和 ARL3T31A/C118F 突变对 ARL3 相关杆-锥体营养不良症患者成纤维细胞线粒体功能的影响。我们的研究结果表明,这些突变导致线粒体呼吸减少、线粒体活性氧(ROS)积累增加,并诱导成纤维细胞凋亡。此外,我们还比较分析了 ARL3T31A、ARL3C118F 和 ARL3T31A/C118F 蛋白对 ARPE-19 细胞线粒体的影响。结果表明,ARL3T31A 和 ARL3T31A/C118F 不仅会影响线粒体功能,还会诱导 ARPE-19 细胞凋亡。相反,ARL3C118F 主要影响细胞凋亡,对 ARPE-19 细胞线粒体功能的影响极小。转录组分析进一步表明,ARL3T31A/C118F 细胞参与了呼吸电子传递、对 ROS 的反应和凋亡信号通路。我们的研究表明,ARL3相关突变在线粒体功能的多样性中起着重要作用,为ARL3相关突变的功能分析提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial functional impairment in ARL3-mutation related rod-cone dystrophy

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.

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来源期刊
FASEB bioAdvances
FASEB bioAdvances Multiple-
CiteScore
5.40
自引率
3.70%
发文量
56
审稿时长
10 weeks
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