线粒体ROS诱导的代谢变化差异调节铁灭的敏感性
bioRxiv : the preprint server for biology
|January 9, 2026
概括
线粒体反应性氧物种 (mtROS) 促进细胞死亡途径铁亡. 这项研究揭示了mtROS抑制了谷氨和辅酶Q10的生物合成,影响肝细胞和癌细胞中的ferroptosis敏感性.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 代谢过程中的代谢.
背景情况:
- 铁化是一种由铁催化,依赖脂质过氧化的细胞死亡过程.
- 线粒体反应性氧物种 (mtROS) 对铁亡的执行至关重要,但其精确的机制尚未完全理解.
研究的目的:
- 为了研究mTROS-依赖的代谢变化,影响铁亡的敏感性.
- 阐明谷氨和辅酶Q10 (CoQ) 生物合成在mtROS介导铁中所起的作用.
主要方法:
- 使用了肝细胞模型和RNA测序 (RNA-seq) 分析.
- 进行基因沉默和过度表达辅酶Q10生物合成基因 (CoQ8A).
- 评估了Farnesoid X受体 (FXR) 和视网状 X受体 (RXRs) 的参与.
主要成果:
- 升高的mtROS和脂质过氧化抑制了糖解,脂肪酸氧化和酸循环.
- mtROS损害了谷氨生物合成和降低了CoQ生物合成基因的调节,包括CoQ8A.
- 沉默CoQ8A增加了铁亡,而其过度表达降低了铁亡的易感性.
结论:
- mtROS促进铁,部分通过抑制谷氨和CoQ生物合成.
- CoQ8A作为ferroptosis易受性的关键调节者.
- 由mtROS介导的CoQ8A下调取决于FXR和RXR信号通路.
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