在管状上皮细胞中,CUL3通过MRPL12无化诱导线粒体功能障碍
Xingzhao Ji1,2,3,4, Xiaoli Yang1, Xia Gu5
1Key Laboratory of Cell Metabolism in Medical and Health of Shandong Provincial Health Commission, Jinan central hospital, Shandong University, Jinan, China.
The FEBS journal
|August 1, 2023
概括
糖尿病病 (DKD) 涉及线粒体功能障碍. 研究人员发现,Cullin3 (CUL3) 向MRPL12,在高葡萄糖条件下损害线粒体生物合成,这表明DKD的新治疗点.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 糖尿病病 (DKD) 是糖尿病的主要并发症,也是慢性病和死亡的主要原因.
- 驱动DKD病变的确切机制,特别是涉及线粒体功能,尚未完全阐明.
研究的目的:
- 研究线粒体核糖体蛋白L12 (MRPL12) 在DKD病变发生过程中的作用.
- 探索Cullin3 (CUL3) 在高葡萄糖条件下调节MRPL12和线粒体功能的参与.
主要方法:
- 利用管状上皮细胞来研究MRPL12的无化.
- 使用生化分析研究了CUL3和MRPL12之间的相互作用.
- 研究了高葡萄糖对CUL3表达,MRPL12无化和线粒体生物合成的影响.
- 评估了CUL3淘汰对MRPL12稳定性和线粒体功能的影响.
主要成果:
- 在管状上皮细胞中,MRPL12主要在K150处无处不在.
- 库林3 (CUL3) 直接与MRPL12相互作用,促进K63相关的无化,并损害线粒体生物合成.
- 高葡萄糖条件上调CUL3,增加MRPL12无化,并破坏线粒体生物合成.
- 在高葡萄糖下,CUL3敲击稳定了MRPL12并保持了线粒体生物合成.
结论:
- 通过CUL3介导的MRPL12的泛基化破坏了管状上皮细胞中的线粒体生物合成.
- 这一途径代表了一种新的机制,有助于DKD.
- 针对CUL3-MRPL12相互作用可能为糖尿病病提供潜在的治疗策略.
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