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利用线粒体到核仁迁移探针点亮核仁以报告线粒体损伤。

Lighting Up Nucleolus To Report Mitochondria Damage Using a Mitochondria-to-Nucleolus Migration Probe.

机构信息

State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.

Shenzhen Research Institute of Shandong University, Shenzhen 518057, China.

出版信息

Anal Chem. 2024 Jun 18;96(24):9808-9816. doi: 10.1021/acs.analchem.3c05629. Epub 2024 Jun 4.

DOI:10.1021/acs.analchem.3c05629
PMID:38833718
Abstract

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

摘要

线粒体状态的可视化对于跟踪细胞生命过程和诊断疾病至关重要,而能够准确评估线粒体状态的荧光探针目前却十分匮乏。在此,我们设计并制备了一种名为“”的荧光探针,它可以通过线粒体膜电位靶向线粒体。在病理或外部刺激下,探针可以从线粒体中释放出来并积累在核仁中,以监测线粒体的状态。在此过程中,核仁的亮度可以作为线粒体损伤的指标。该探针在活细胞中表现出优异的光稳定性,并且对生物活性分子和活细胞的生理 pH 环境具有极其惰性的荧光响应。光谱滴定和分子对接研究表明,探针可以在核仁中被点亮,这是由于细胞核的高粘度和与 RNA 磷酸骨架的强静电相互作用。基于其在活细胞中线粒体状态跟踪方面的优异成像性能,该探针有望成为一种卓越的工具。

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