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Nano Research

Article Title

Nanoscale monitoring of mitochondria and lysosome interactions for drug screening and discovery

Authors

Qixin Chen, School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China Shandong Academy of Pharmaceutical Science, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Xintian Shao, School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China Shandong Academy of Pharmaceutical Science, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Zhiqi Tian, Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Yang Chen, Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Payel Mondal, Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Fei Liu, School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China Shandong Academy of Pharmaceutical Science, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
Fengshan Wang, School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China
Peixue Ling, School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China Shandong Academy of Pharmaceutical Science, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
Weijiang He, State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
Kai Zhang, Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Zijian Guo, State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
Jiajie Diao, Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

Keywords

drug screening, mitochondria, lysosome, mitophagy, structured illumination microscopy

Abstract

Technology advances in genomics, proteomics, and metabolomics largely expanded the pool of potential therapeutic targets. Compared with the in vitro setting, cell-based screening assays have been playing a key role in the processes of drug discovery and development. Besides the commonly used strategies based on colorimetric and cell viability, we reason that methods that capture the dynamic cellular events will facilitate optimal hit identification with high sensitivity and specificity. Herein, we propose a live-cell screening strategy using structured illumination microscopy (SIM) combined with an automated cell colocalization analysis software, CellprofilerTM, to screen and discover drugs for mitochondria and lysosomes interaction at a nanoscale resolution in living cells. This strategy quantitatively benchmarks the mitochondria-lysosome interactions such as mitochondria and lysosomes contact (MLC) and mitophagy. The automatic quantitative analysis also resolves fine changes of the mitochondria-lysosome interaction in response to genetic and pharmacological interventions. Super-resolution live-cell imaging on the basis of quantitative analysis opens up new avenues for drug screening and development by targeting dynamic organelle interactions at the nanoscale resolution, which could facilitate optimal hit identification and potentially shorten the cycle of drug discovery.

Graphical Abstract

Publisher

Tsinghua University Press

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