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在AML12肝细胞模型中,AUF1通过维持线粒体平衡来抑制肝细胞衰老

Myeongwoo Jung^1,2, Sukyoung Han^1,3, Seungyeon Ryu^1,3

¹Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

|January 9, 2026

概括

通过维护线粒体健康,RNA结合蛋白AUF1 (hnRNP D) 限制了细胞衰老. 较低的AUF1水平加速衰老,而其恢复保留了线粒体功能并抑制了衰老轴.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
衰老研究研究衰老研究

背景情况:

细胞衰老,一个关键的衰老过程,涉及增长停止和改变的分泌表型 (SASP).
衰老经常与线粒体功能障碍和器官间通信障碍有关.
在衰老和线粒体平衡中RNA结合蛋白AUF1 (hnRNP D) 的作用尚不清楚.

研究的目的:

研究AUF1在调节肝细胞细胞衰老和线粒体功能中的作用.
阐明AUF1在衰老期间影响线粒体动力学和器官间通信的分子机制.

主要方法:

在AML12肝细胞中利用慢性氧化应激模型诱导细胞衰老.
使用规范标记评估衰老 (SA β-gal阳性,增殖停止).
进行了AUF1淘汰和宫外表达研究,分析了线粒体形态,膜潜力,ATP水平,ROS产生和线粒体-ER合.

主要成果:

在衰老的肝细胞中,AUF1水平下降.
AUF1的淘汰加剧了衰老,导致线粒体网络延长,减少了膜潜力,减少了ATP和增加了ROS.
AUF1倒置损害了线粒体-ER合,并降低了线粒体Ca2+负载.
AUF1直接与Opa1和Mfn2 3'UTRs结合,调节它们的表达并影响线粒体动态.
异位AUF1表达恢复了衰老细胞中的线粒体结构和生物能功能.

结论:

AUF1在维护线粒体平衡和抑制肝细胞中线粒体衰老轴方面发挥着至关重要的作用.
AUF1在转录后作用,调节线粒体动态蛋白Opa1和Mfn2.
准AUF1或其下游途径可能为与年龄相关的疾病提供治疗策略.

关键词:

在AUF1中,AUF1是AUF1.融合融合融合融合融合融合融合融合融合线粒体中的线粒体.有活性氧物种的反应性氧物种.衰老是一种老化.

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