A dual-labeling probe to track functional mitochondria–lysosome interactions in live cells

Qixin Chen, Hongbao Fang, Xintian Shao, Zhiqi Tian, Shanshan Geng, Yuming Zhang, Huaxun Fan, Pan Xiang, Jie Zhang, Xiaohe Tian, Kai Zhang (), Weijiang He (), Zijian Guo () and Jiajie Diao ()
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Qixin Chen: Nanjing University
Hongbao Fang: Nanjing University
Xintian Shao: University of Cincinnati College of Medicine
Zhiqi Tian: University of Cincinnati College of Medicine
Shanshan Geng: Nanjing University
Yuming Zhang: Nanjing University
Huaxun Fan: University of Illinois at Urbana-Champaign
Pan Xiang: Anhui University
Jie Zhang: Shandong University
Xiaohe Tian: Anhui University
Kai Zhang: University of Illinois at Urbana-Champaign
Weijiang He: Nanjing University
Zijian Guo: Nanjing University
Jiajie Diao: University of Cincinnati College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-20067-6

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