脂质化依赖于费雷多克辛FDX1,在人体细胞中缺氧的情况下可用
Pallavi R Joshi1, Shayan Sadre1, Xiaoyan A Guo1
1Broad Institute, Cambridge, Massachusetts, USA; Department of Molecular Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
The Journal of biological chemistry
|July 22, 2023
概括
铁素1 (FDX1) 对于脂酸合成至关重要,但在低氧条件下对细胞生长不需要. 缺氧使细胞能够容忍脂肪酸的损失,揭示出不同的铁素作用.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 线粒体功能的功能
背景情况:
- 铁硫集群 (ISC) 是许多细胞过程中的重要辅因子.
- 铁毒素 (FDX) 是古代含有ISC的蛋白质,参与电子转移.
- 人类线粒体含有FDX1和FDX2,FDX2在ISC合成中发挥作用.
研究的目的:
- 在低氧条件下研究FDX1和FDX2在人体细胞中的作用.
- 为了确定FDX1是否对脂酸合成至关重要.
- 探索缺氧对细胞对脂酸缺乏症耐受性的影响.
主要方法:
- 培养的人类细胞被 subjected to normoxic 和 hypoxic (1% O2) 条件.
- 使用了FDX1和基合成酶的基因淘汰 (KO) 模型.
- 评估了细胞生长表型和化状态.
主要成果:
- FDX1,但不是FDX2,在缺氧下对细胞生长是不可或缺的.
- FDX1对于酸辅因子的合成至关重要.
- 低氧在FDX1或基合成酶KO细胞中挽救了生长缺陷,但不是基化.
结论:
- 在线粒体中,FDX1和FDX2具有不同的作用.
- FDX1对于脂酸生物合成至关重要.
- 细胞可以在低氧条件下容忍缺乏脂酸,这表明代谢适应.
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