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线粒体蛋白NDUFS8对血管生成的要求
Qian-Wei Xiong1, Kun Jiang2, Xiao-Wei Shen3
1Department of Urology Surgery, Children's Hospital of Soochow University, Suzhou, China.
Cell death & disease
|April 9, 2024
概括
线粒体蛋白NDUFS8对于内皮细胞激活和血管生成至关重要. 它的枯竭会损害线粒体功能,阻碍血管形成,而它的过度表达则会促进它.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 血管新生研究研究
背景情况:
- 线粒体对于内皮细胞功能和血管生成至关重要.
- 线粒体复合体I的核心子单元NDUFS8,对复合体I活动至关重要.
研究的目的:
- 研究NDUFS8在内皮细胞激活和血管生成中的作用.
- 阐明NDUFS8在这些过程中的功能背后的分子机制.
主要方法:
- 利用shRNA和CRISPR/Cas9使NDUFS8在内皮细胞中沉默或淘汰.
- 评估了线粒体功能,细胞增殖,迁移和毛细管形成.
- 研究了Akt-mTOR信号通路,并进行了体内视网膜血管生成试验.
- 在人类增殖性糖尿病视网膜病变组织中分析了NDUFS8表达.
主要成果:
- NDUFS8的枯竭损害了线粒体功能,减少了ATP的产生,增加了氧化应激,并阻碍了细胞的增殖,迁移和管形成.
- NDUFS8的敲除抑制了Akt-mTOR通路,该通路通过Akt的重新激活被挽救.
- 在体内,NDUFS8的淘汰抑制了视网膜血管生成,并诱导了线粒体功能障碍.
- 在人类增殖性糖尿病视网膜病变组织中观察到高NDUFS8表达.
结论:
- NDUFS8是内皮细胞激活和血管生成的关键调节者.
- NDUFS8的功能与线粒体复合体I活动和Akt-mTOR通路有关.
- NDUFS8代表了血管生成相关疾病的潜在治疗标.
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