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在人类肌肉中,BMAL1和CLOCK蛋白与线粒体动力学,蛋白质合成途径和肌肉力量具有差异性关联

A M Figueroa-Toledo¹, J Gutiérrez-Pino¹, A Carriel-Nesvara¹

¹Laboratorio de Fisiología del Ejercicio y Metabolismo (LABFEM), Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile.

The Journal of physiology

|June 26, 2024

概括

骨肌肉 (SkM) 蛋白质BMAL1和CLOCK影响男性的线粒体健康和功能. 较低的BMAL1与较小的线粒体和减少的mTOR有关,而较低的CLOCK与线粒体动力学受损和SkM强度降低有关.

科学领域:

人类生理学人类生理学
分子生物学分子生物学
线粒体动力学的动态

背景情况:

减少了CLOCK/BMAL1蛋白质的小鼠模型显示骨肌肉 (SkM) 恶化和线粒体异常.
较低的CLOCK/BMAL1蛋白水平对人类SkM功能和线粒体健康的影响在很大程度上仍未被探索.

研究的目的:

研究BMAL1和CLOCK蛋白水平与线粒体动力学,分子标记物和男性人类SkM的功能质量之间的关联.

主要方法:

来自16名健康男性的骨肌肉活检分析了线粒体形态,蛋白质丰富度 (OXPHOS,融合/裂变调节器,线粒体,蛋白质合成信号) 和SkM质量 (截面面积,最大强度).
传输电子显微镜被用来评估线粒体-质细胞网膜相互作用和形态.
西方涂抹量化了与线粒体功能和肌肉蛋白质合成相关的蛋白质水平.

主要成果:

BMAL1蛋白质质量与线粒体-SR距离,线粒体大小,晶状体密度和mTOR蛋白质质量正相关.
时钟蛋白质质量与线粒体-SR相互作用有负面关联,但与线粒体复合物III,OPA1和DRP1蛋白水平有积极关联.
时钟蛋白质质量也与蛋白质合成途径 (mTOR,AKT,P70S6K) 和SkM强度有关.

结论:

在人类男性中,BMAL1和CLOCK蛋白在调节线粒体动力学和SkM功能方面发挥着不同的作用.
这些发现表明,准BMAL1和CLOCK调制可能为肌肉疾病和代谢障碍提供治疗潜力.

关键词:

昼夜时钟是生物周期的时间表.线粒体晶状体的密度密度线粒体的融合和裂变.线粒体sarcoplasmic网膜的相互作用.线粒细胞衰变 (mitophagy) 是一种神经衰变的过程.肌肉的力量肌肉的力量肌肉的力量

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