MARCH5通过RACGAP1-DRP1相关的线粒体质量控制改善了大动脉的化
Jialiang Zhang1, Yaoyu Zhang2, Wenhua Lei2
1Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu 610041, PR China; Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Biochimica et biophysica acta. Molecular cell research
|January 29, 2025
概括
线粒体E3泛素酶MARCH5缺乏会损害线粒体质量控制,通过激活RACGAP1和DRP1.1,促进大动脉的化. 恢复MARCH5或抑制RACGAP1可能会带来治疗效益.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体生物学 线粒体生物学
- 细胞应激反应的应激反应
背景情况:
- 线粒体E3泛素化酶 (MARCH5) 对于线粒体功能至关重要.
- 大动脉结石化 (AVC) 涉及线粒体质量控制受损.
- 目前尚不清楚MARCH5在AVC病原发生中的具体作用.
研究的目的:
- 研究MARCH5在大动脉结石化中的作用和潜在机制.
- 探索MARCH5之间的关系,线粒体动力学和膜细胞中的骨质分化.
主要方法:
- 分析了人类大动脉中的MARCH5表达.
- 在人类大动脉膜间歇细胞 (HVICs) 中评估了线粒体形态,骨质分化和氧化酸化.
- 在体内研究中使用了MARCH5-knockdown和ApoE-knockout小鼠模型.
主要成果:
- 在化门中,MARCH5蛋白水平下降,与线粒体质量控制受损相关.
- 在HVICs中,MARCH5抑制加速了骨质转化,而过度表达具有保护作用.
- MARCH5与RACGAP1相互作用,促进其无处不在,导致DRP1激活和线粒体功能障碍. 抑制RACGAP1逆转了MARCH5沉默引起的化.
结论:
- 降低MARCH5的调节促进RACGAP1的无化和DRP1的激活,损害了线粒体质量控制,并导致大动脉结石化.
- MARCH5-RACGAP1-DRP1轴代表了大动脉结石化的潜在治疗标.
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