依赖谷氨酸的Slc25a39-Nrf2轴配对线粒体动力学与代谢重编程以建立肌源性承诺
Brian Kelly1, Chia-Hua Wu1, Kaan I Eskut1
1Department of Biology, University of Kentucky, Lexington, Kentucky 40502, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
骨肌肉的再生需要神经细胞来感知谷氨酸的可用性. 脱离谷氨胺会诱导一种可逆的平衡代谢停止 (PMA) 状态,保持差异化潜力.
科学领域:
- 细胞生物学 细胞生物学
- 肌肉再生 肌肉再生
- 代谢调节 代谢调节 代谢调节 代谢调节
背景情况:
- 肌源性承诺对于骨肌肉再生至关重要.
- 氨基酸,特别是谷氨胺,通过将新陈代谢和基因表达联系起来,影响这个过程.
- 髓质细胞必须感知营养的可用性,以便进行适当的进展.
研究的目的:
- 研究谷氨胺禁用对肌肉细胞的分子后果.
- 确定由谷氨胺限制诱导的细胞机制和状态.
- 确定谷氨胺感应在肌体承诺和分化中的作用.
主要方法:
- 在神经细胞中进行了急性谷氨胺戒断实验.
- 代谢途径的分析 (糖解,氧化).
- 线粒体形态和功能评估 (裂变,脱极化).
- 转录形状分析 (基因表达分析).
- 对氧化还原平衡和谷氨途径的研究.
主要成果:
- 谷氨胺氧化支持糖解,线粒体裂变和氧化还原平衡,用于肌体承诺.
- 脱离谷氨胺会引发还原性转移,线粒体延长和生长停止.
- 诱导一种可逆的平衡代谢停止 (PMA) 状态,其特征是特定的基因表达变化.
- PMA是由Nrf2-依赖的谷氨生物合成和Slc25a39上调调节的介导.
- Slc25a39和线粒体谷氨对于维持PMA和分化潜力至关重要.
结论:
- 肌细胞感知到谷氨胺的可用性,以调节向肌细胞承诺的进展.
- 均衡代谢停止 (PMA) 是一种依赖谷氨酸的检查点,可以保持分化能力.
- 一个Slc25a39-Nrf2氧化还原轴将谷氨酸感应与线粒体和代谢适应用于肌肉再生.
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