Aggregation‐based dual‐target probe for dual‐colour super‐resolution monitoring mitophagy and evaluating drugs regulating mitochondria

Aggregate Pub Date : 2024-09-10 DOI:10.1002/agt2.641
Xiu‐Zhi Yang, Hongbao Fang, Shumeng Li, Chengyan Chu, Yunhua Zhang, Ying Yang, Weijiang He, Yuncong Chen, Zijian Guo
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Abstract

Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super‐resolution is highly demanded yet quite challenging. Herein, a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour, respectively. AHOH could be selectivity oxidized by HClO, leading to a large emission blue shift (90 nm) and an over 1300‐fold enhancement of the emission ratio of Fl547nm/Fl637nm. We apply AHOH in super‐resolution microscopy and clearly visualize the dynamics of mitochondria–lysosomes interactions and the oxidative stress states upon different stimuli. Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy. Moreover, AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction. This work provides a powerful dual‐colour super‐resolution imaging agent for real‐time monitoring the dynamics of organelle interactions and oxidative stress.

Abstract Image

基于聚集的双目标探针,用于双色超分辨率监测有丝分裂和评估调控线粒体的药物
开发能同时以超分辨率观察有丝分裂通量和氧化应激的单一荧光探针是非常有必要的,但也相当具有挑战性。在此,我们设计并合成了一种可同时对溶酶体和线粒体分别进行红色和绿色染色的 HClO 比率探针 AHOH。AHOH 可被 HClO 选择性氧化,从而产生较大的发射蓝移(90 nm),并使 Fl547nm/Fl637nm 的发射比增强 1300 倍以上。我们将 AHOH 应用于超分辨率显微镜,清晰地观察了线粒体-溶酶体相互作用的动态以及不同刺激下的氧化应激状态。不同药物和基因缺陷引发的线粒体功能障碍会导致氧化应激升高和丝裂吞噬水平升高。此外,AHOH 可以作为评估调节线粒体功能障碍药物疗效的可靠工具。这项工作为实时监测细胞器相互作用和氧化应激的动态提供了一种功能强大的双色超分辨率成像剂。
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