通过非典型的cadherin Fat1控制线粒体功能和细胞生长
Longyue L Cao1,2, Dario F Riascos-Bernal1,2, Prameladevi Chinnasamy1,2
1Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nature
|November 10, 2016
概括
非典型的Fat1干作为线粒体制动剂,控制血管光滑肌肉细胞的增殖. 脂肪1的损失加速细胞生长和线粒体呼吸,影响血管修复和潜在的其他疾病.
科学领域:
- 细胞代谢
- 线粒体生物学
- 血管生物学
背景情况:
- 线粒体功能障碍会影响生长,衰老以及癌症和心血管疾病等疾病.
- 线粒体活动的生理调节者尚未完全理解.
- 血管光滑肌细胞 (SMC) 增殖对于动脉损伤后的组织修复至关重要.
研究的目的:
- 调查非典型的Fat1cadherin在调节线粒体呼吸和SMC增殖中的作用.
- 确定Fat1的生长调节功能是否与线粒体固有.
主要方法:
- 使用Fat1淘汰 (Fat1^KO) 鼠标模型和SMC.
- 分析了线粒体呼吸,氧气消耗和酸盐水平.
- 检查了Fat1蛋白位址和线粒体内的相互作用.
- 评估了线粒体呼吸复合体活动和超复合体形成.
- 在受伤的人类和小鼠动脉中研究Fat1表达和功能.
主要成果:
- 脂肪1碎片积聚在SMC线粒体中,与线粒体蛋白相互作用.
- 脂肪1^KOSMC表现出增加的增殖,氧气消耗和酸盐水平.
- 细胞内Fat1域的线粒体定位部分恢复了正常的氧气消耗.
- 脂肪1删除增强了线粒体呼吸复合体I和II活动和超复合体形成.
- 在小鼠中,特定于SMC的Fat1无活化加剧了血管损伤反应,增加了增生和新极端生长.
结论:
- 脂肪1作为线粒体呼吸的分子制动剂,抑制SMC的扩散.
- 这种Fat1介导的生长控制是线粒体内在的.
- 在血管修复过程中,Fat1在调节细胞生长中发挥着关键作用.
- 控制线粒体活动的Fat1功能可能与癌症和发育障碍有关.
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