分子核蛋白失衡作为一个保存长寿机制
Riekelt H Houtkooper1, Laurent Mouchiroud, Dongryeol Ryu
1Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Nature
|May 24, 2013
概括
线粒体核糖体蛋白 (MRPs) 通过控制核和线粒体蛋白之间的平衡来调节寿命. 破坏这种平衡会激活一种关键的长寿途径,这种途径在各个物种中得到保护.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 长寿受到相互连接的代谢途径的影响.
- 线粒体功能在衰老和寿命调节中起着至关重要的作用.
研究的目的:
- 确定新陈代谢和寿命的关键调节者.
- 研究线粒体核糖体蛋白 (MRPs) 在衰老中的作用.
主要方法:
- 鼠群遗传学和RNA干扰在Caenorhabditis elegans中.
- 使用抗生素和乙基化物进行药理操作.
- 对线粒子核蛋白失衡和线粒体未折叠蛋白反应 (UPRmt) 的分析.
主要成果:
- 线粒体核糖体蛋白S5 (Mrps5) 和其他MRPs被确定为长寿调节剂.
- 镇压MRPs诱导了线核蛋白失衡,减少了呼吸,并激活了UPRmt.
- 抗生素,乙基化物,白醇和拉巴胺模仿了MRP的淘汰效应,通过诱导线核失衡和UPRmt.延长寿命.
结论:
- MRPs是进化保守的调节者,将线粒体核糖体与长寿途径联系起来.
- 分子核蛋白失衡和UPRmt是延长寿命的保守机制.
- 准线粒体翻译和转录可以调节衰老.
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