在肌肉前体细胞中遗传的肌源性能力是由线粒体复合体I编码蛋白质定义的
Norio Motohashi1, Katsura Minegishi2, Yoshitsugu Aoki3
1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, 187-8502, Japan. nmotohashi@ncnp.go.jp.
Cell death & disease
|October 19, 2023
概括
肌源性细胞潜力取决于肌肉区域,而不是纤维类型. 线粒体基因Ndufs8影响细胞功能并随着年龄的增长而下降,但NAD+补充可能会改善衰老的肌肉细胞.
科学领域:
- 肌肉生理学 肌肉生理学
- 细胞生物学 细胞生物学
- 线粒体功能 线粒体功能
背景情况:
- 骨肌的卫星细胞 (SCs) 有不同的肌源性质.
- 以前的研究表明,慢型肌肉衍生的肌肉细胞 (MBs) 比快型更好地自我更新.
- 肌肉纤维类型对肌肉区域对肌体细胞功能的影响尚不清楚.
研究的目的:
- 为了调查肌源性细胞功能是否与肌肉纤维类型或区域有关.
- 为了识别来自慢 (SOL) 和快 (TA) 肌肉区域的MBs之间的分子差异.
- 探索线粒体复合体I在MB衰老和功能中的作用.
主要方法:
- 全球基因表达分析.
- 来自SOL和TA肌肉的MBs的蛋白质组分析.
- 对于 Ndufs8.8 的功能增益和丧失实验.
- 测量NAD/NADH比率和p53乙化.
- 在体内实验中使用尼古丁胺胺单核酸治疗.
主要成果:
- 肌源性潜力取决于区域,而不是纤维类型.
- 在SOL衍生的MB中,NADH脱酶 (ubiquinone) 铁硫蛋白8 (Ndufs8) 的含量较高,并且随着年龄的增长而降低.
- Ndufs8促进了MB分化,自我更新和对亡的抵抗.
- 抑制ndufs8导致p53乙化增加和降低NAD/NADH比率.
- 尼古丁胺胺单核酸治疗恢复了NAD+水平,减少了p53乙化,并改善了自我更新.
结论:
- 在MBs中的功能差异是由线粒体复合体I基因控制的.
- 与SC数的与衰老相关的下降与Ndufs8表达相关.
- 补充NAD+是一种潜在的策略,可以抵消与年龄相关的肌细胞功能下降.
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