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Nano Research 2019, 12(5): 1009-1015 https://doi.org/10.1007/s12274-019-2331-x
Research Article | Issue | Published: 11 March 2019

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

Show Author's Information Qixin Chen1,2,3,  Xintian Shao1,2,3,  Zhiqi Tian3,  Yang Chen3,  Payel Mondal4,  Fei Liu1,2,  Fengshan Wang1,  Peixue Ling1,2( ),  Weijiang He5( ),  Kai Zhang4,  Zijian Guo5,  Jiajie Diao3( )
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
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
State Key Laboratory of Coordination Chemistry,Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University,Nanjing,210093,China;
Keywords:
mitochondria, drug screening, lysosome, mitophagy, structured illumination microscopy
Topics:
Cell proliferation CytologyMolecular biology
Cite this article:
Chen Q, Shao X, Tian Z, et al. Nanoscale monitoring of mitochondria and lysosome interactions for drug screening and discovery. Nano Research, 2019, 12(5): 1009-1015. https://doi.org/10.1007/s12274-019-2331-x
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Abstract Full text Electronic supplementary material About this article

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.


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Electronic supplementary material
About this article

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

Show Author's information Qixin Chen1,2,3, Xintian Shao1,2,3, Zhiqi Tian3, Yang Chen3, Payel Mondal4, Fei Liu1,2, Fengshan Wang1, Peixue Ling1,2( ), Weijiang He5( ), Kai Zhang4, Zijian Guo5, Jiajie Diao3( )
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
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
State Key Laboratory of Coordination Chemistry,Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University,Nanjing,210093,China;

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.

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

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Publication history
Copyright
Acknowledgements

Publication history

Received: 25 October 2018
Revised: 03 February 2019
Accepted: 04 February 2019
Published: 11 March 2019
Issue date: May 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

Acknowledgements

This research was supported by the National Basic Research Program of China (No. 2015CB856300), Natural Science Foundation of Shandong Province (Nos. ZR2017PH072, ZR2017BH051, and ZR2015QL007), and Key Research and Development Plan of Shandong Province (No. 2018GSF121033). K. Z. was supported by the University of Illinois at Urbana-Champaign. The Light Microscopy Imaging Center (LMIC) is supported in part with funds from Indiana University Office of the Vice Provost for Research. The 3D-SIM microscope was provided by NIH grant NIH1S10OD024988-01.

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