MOTS-c通过直接结合和激活CK2来调节骨肌肉功能
Hiroshi Kumagai1, Su-Jeong Kim1, Brendan Miller1
1The Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
iScience
|November 19, 2024
概括
线粒体微蛋白MOTS-c激活蛋白激酶CK2,改善新陈代谢和预防肌肉缩. 这种互动对MOTS-cc至关重要.
科学领域:
- 线粒体生物学 线粒体生物学
- 代谢调节 代谢调节 代谢调节
- 老龄化的分子机制.
背景情况:
- 12S rRNA-c (MOTS-c) 的线粒体开放读取框架是一种调节新陈代谢并对抗与年龄相关的疾病的类激素.
- 确切的分子标和MOTS-c有益作用的基础机制仍然不完全理解.
研究的目的:
- 识别和功能性地描述MOTS-c.的直接分子标.
- 阐明这些目标在调解MOTS-c对新陈代谢和肌肉健康的生理影响中的作用.
主要方法:
- 在体外结合测试以评估MOTS-c与候选蛋白的相互作用.
- 无细胞激酶测试以确定MOTS-c对蛋白激酶活性的影响.
- 使用小鼠模型进行体内研究,以评估MOTS-c给药和CK2抑制对骨肌肉和葡萄糖代谢的影响.
- 对脂肪和肌肉组织的组织特异性影响和分子相互作用的分析.
- 研究一种自然存在的MOTS-c变体 (K14Q MOTS-c) 和其功能后果.
主要成果:
- MOTS-c直接与蛋白激酶CK2 (素激酶2) 结合并激活.
- 在小鼠中使用MOTS-c可以预防骨肌肉缩和增强葡萄糖吸收,其效果取决于CK2活性.
- MOTS-c表现出组织特异性作用,激活肌肉中的CK2,但抑制脂肪中的CK2.
- 一种自然存在的变体,K14Q MOTS-c,显示了减少的CK2结合,缺乏MOTS-c的生理效应.
- 携带K14Q MOTS-c的男性携带者患上了缩症和2型糖尿病 (T2D) 的风险增加,而女性则表现出特定于年龄的T2D风险降低.
结论:
- 蛋白激酶CK2是MOTS-c.的代谢和抗缩作用所需的直接和功能性标.
- 在不同的组织中,MOTS-c对CK2的不同调节有助于其组织特异性的作用.
- 自然发生的MOTS-c变体与受损的CK2相互作用可能会影响对代谢障碍和肉症的易感性.
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