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线粒体tRNA特异性的牛素修饰与与铁亡相关的肌心损伤相关

Yu Pan¹, Jin-Jie Hu¹, Xiao-Rong Ma¹

¹State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.

Journal of molecular biology

|May 21, 2025

概括

线粒体转移RNA (tRNA) 上的氨酸修饰在心脏损伤期间的铁亡中至关重要. 这些修饰的下调会使铁亡恶化,而它们的恢复则提供保护.

科学领域:

生物化学生物化学
分子生物学分子生物学
心血管研究研究心血管研究

背景情况:

转移RNA (tRNA) 修改对于细胞功能和应激反应至关重要.
铁亡是一种受调节的细胞死亡形式,在缺血性心肌损伤中起作用,但其与tRNA表转录组的联系尚不清楚.

研究的目的:

为了研究铁亡相关心肌损伤期间tRNA修饰的动态变化.
阐明特定tRNA修饰在心肌细胞铁亡中的作用.

主要方法:

使用基于液态染色学和质谱学 (LC-MS) 的RNA映射平台.
检查了40个tRNA修饰在铁亡相关的心肌损伤模型.
在体外和体内研究了 taurine 修饰耗尽和恢复的影响.

主要成果:

在八个tRNA修改中发现了显著的变化,在线粒体tRNAs (mt-tRNATrp,mt-tRNAGln) 的第34位反点上, taurine修改 (τm5U, τm5s2U) 显著减少.
铁致死诱导剂RSL3通过食用牛素导致牛素修饰耗尽,并降低了MTO1和GTPBP3的表达.
taurine 修饰物的耗尽加剧了铁亡,而恢复通过减少活性氧物种和脂质过氧化物而提供了保护.

结论:

线粒体tRNA上的氨酸修饰对于在心肌细胞铁亡过程中确定细胞命运至关重要.
这项研究为tRNA表写体在铁亡相关的缺血性心肌损伤中的作用提供了新的见解.

关键词:

铁性化 (ferroptosis) 是一种心肌损伤是指心肌损伤.tRNA的修改 tRNA的改变 taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine taurine 是一种类型的蛋白质,其含量很大.

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