延长因子1A1调节哺乳动物细胞中的代谢基质偏好
Rachel B Wilson1, Alexandra M Kozlov2, Helia Hatam Tehrani1
1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
The Journal of biological chemistry
|January 25, 2024
概括
细胞延长因子1A1 (EEF1A1) 调节细胞代谢. 其缺乏将细胞转向脂肪酸氧化,影响糖解和脂质含量,揭示了新型的代谢基质偏好作用.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 分子生物学分子生物学
背景情况:
- 细胞延长因子1A1 (EEF1A1) 已知用于蛋白质合成,但具有其他细胞作用.
- 以前的工作将EEF1A1与脂毒性和肝脏脂质积累联系起来.
- 这表明EEF1A1和代谢调节之间存在联系.
研究的目的:
- 研究EEF1A1在调节代谢基质偏好的作用.
- 了解EEF1A1如何影响糖解和氧化代谢.
主要方法:
- 使用了EEF1A1缺陷的中国仓鼠卵巢 (2E2) 细胞和EEF1A1在HepG2细胞中的敲除.
- 采用细胞外流量分析来评估代谢表型.
- 利用RNA-seq,免疫阻塞和酶活性测试来分析基因和蛋白质表达.
- 用EEF1A抑制剂治疗的细胞 (迪德姆宁B,普利蒂素).
主要成果:
- 缺乏或抑制EEF1A1降低了乳酸盐和糖溶性ATP的产生,有利于氧化代谢.
- 在缺乏EEF1A1的细胞中观察到脂肪酸氧化和中性脂质含量增加.
- 一个关键的糖解酶hexokinase 2的下调显著.
- 通过NFKB和MYC目标下调TNFA信号,减少核RELB和MYC.
结论:
- 在哺乳动物细胞中,EEF1A1在调节代谢基质利用方面发挥作用.
- 通过影响NFKB和MYC介导的基因表达,EEF1A1缺乏会扰乱糖解.
- 这导致赫索金酶表达和活性降低,转移代谢偏好.
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