线粒体中的PRMT5通过TFAM氨酸甲基化调节mtDNA的稳定性
Sangheeta Bhattacharjee1, Sayan Das1, Banhi Chowdhury1
1Laboratory of Molecular Biology, School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India.
Nature communications
|February 23, 2026
概括
蛋白质氨酸甲基转移酶5 (PRMT5) 对于线粒体DNA (mtDNA) 的维护至关重要. 这项研究表明,PRMT5调节TFAM,对mtDNA稳定性和细胞呼吸至关重要.
科学领域:
- 线粒体生物学 线粒体生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 修复DNA的修复DNA的修复
背景情况:
- 蛋白质氨酸甲基转移酶5 (PRMT5) 调节包括扩散和DNA损伤反应在内的核过程.
- 在线粒体中PRMT5的作用及其对线粒体DNA (mtDNA) 稳态的影响在很大程度上仍未被探索.
研究的目的:
- 研究PRMT5.5的线粒体定位和功能.
- 阐明PRMT5在维护线粒体DNA (mtDNA) 完整性和细胞呼吸中的作用.
主要方法:
- 产生和分析PRMT5淘汰细胞.
- 评估mtDNA拷贝数,核细胞数和线粒体形态.
- 通过共免疫沉识别PRMT5相互作用伙伴.
- 对TFAM甲基化状态和稳定性的分析.
主要成果:
- 核编码的PRMT5定位在线粒体中,对mtDNA稳态至关重要.
- 缺少PRMT5导致mtDNA复制数减少,线粒体动力学受损,呼吸功能受损.
- PRMT5直接与TFAM相互作用,催化其在R82的对称二甲基化,这对mtDNA结合和稳定至关重要.
- R82甲基化的损失使TFAM不稳定,导致其被LonP1.1降解.
结论:
- PRMT5作为一个调节mtDNA维护的线粒体酶.
- 通过PRMT5介导的TFAM甲基化是维护mtDNA完整性和细胞功能的关键机制.
- PRMT5的失调会影响线粒体健康和细胞活力.
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