State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Nat Commun. 2020 Dec 8;11(1):6290. doi: 10.1038/s41467-020-20067-6.
Mitochondria-lysosome interactions are essential for maintaining intracellular homeostasis. Although various fluorescent probes have been developed to visualize such interactions, they remain unable to label mitochondria and lysosomes simultaneously and dynamically track their interaction. Here, we introduce a cell-permeable, biocompatible, viscosity-responsive, small organic molecular probe, Coupa, to monitor the interaction of mitochondria and lysosomes in living cells. Through a functional fluorescence conversion, Coupa can simultaneously label mitochondria with blue fluorescence and lysosomes with red fluorescence, and the correlation between the red-blue fluorescence intensity indicates the progress of mitochondria-lysosome interplay during mitophagy. Moreover, because its fluorescence is sensitive to viscosity, Coupa allowed us to precisely localize sites of mitochondria-lysosome contact and reveal increases in local viscosity on mitochondria associated with mitochondria-lysosome contact. Thus, our probe represents an attractive tool for the localization and dynamic tracking of functional mitochondria-lysosome interactions in living cells.
线粒体-溶酶体相互作用对于维持细胞内稳态至关重要。尽管已经开发出各种荧光探针来可视化这种相互作用，但它们仍然无法同时标记线粒体和溶酶体，并动态跟踪它们的相互作用。在这里，我们引入了一种细胞渗透性、生物相容性、粘度响应的小分子有机分子探针 Coupa，以监测活细胞中线粒体和溶酶体的相互作用。通过功能荧光转换，Coupa 可以同时用蓝色荧光标记线粒体，用红色荧光标记溶酶体，而红-蓝荧光强度的相关性表明自噬过程中线粒体-溶酶体相互作用的进展。此外，由于其荧光对粘度敏感，Coupa 使我们能够精确地定位线粒体-溶酶体接触部位，并揭示与线粒体-溶酶体接触相关的线粒体上局部粘度的增加。因此，我们的探针为活细胞中功能线粒体-溶酶体相互作用的定位和动态跟踪提供了一种有吸引力的工具。
