缺氧会诱导线粒体蛋白质的乳糖化,以限制氧化酸化
Yunzi Mao1, Jiaojiao Zhang1, Qian Zhou1
1The Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children's Hospital of Fudan University, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
由缺氧诱导的线粒体蛋白质乳化,通过抑制关键酶来限制ATP的产生. 这一过程涉及AARS2并由SIRT3逆转,通过调节氧化酸化,影响运动表现.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 氧化酸化 (OXPHOS) 产生ATP,但其通过氧气水平的调节尚不清楚.
- 细胞内氧气的可用性对于平衡细胞能量需求至关重要.
研究的目的:
- 阐明平衡OXPHOS活动和细胞内氧的机制.
- 为了确定线粒体蛋白质乳糖化如何在低氧条件下调节OXPHOS.
主要方法:
- 作为乳酸转移酶,研究了线粒体阿兰-tRNA合成酶 (AARS2).
- 研究了PHD2在AARS2降解和缺氧诱导的乳糖化中的作用.
- 评估了PDHA1和CPT2乳化对酶活性和OXPHOS的影响.
- 研究了乳化对小鼠运动期间肌肉细胞功能的影响.
主要成果:
- 由AARS2介导的线粒体蛋白质乳化,由低氧诱导,以抑制OXPHOS.
- 缺氧导致AARS2的积累,乳化PDHA1和CPT2,从而限制了乙-CoA的流入.
- 通过SIRT3,PDHA1和CPT2的乳化是可逆的,SIRT3激活了OXPHOS.
- 在小鼠肌肉细胞中的乳化通过限制OXPHOS来限制耐力炼能力.
结论:
- 线粒体蛋白质的乳酸化作为OXPHOS的关键调节者,对细胞内缺氧的反应起作用.
- AARS2-乳糖化途径集成了缺氧和乳酸信号,以控制细胞能量代谢.
- 调节乳糖化水平可以影响代谢灵活性和运动表现.
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