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

被引:50
作者
Chen, Qixin [1 ,2 ,3 ]
Shao, Xintian [1 ,2 ,3 ]
Tian, Zhiqi [3 ]
Chen, Yang [3 ]
Mondal, Payel [4 ]
Liu, Fei [1 ,2 ]
Wang, Fengshan [1 ]
Ling, Peixue [1 ,2 ]
He, Weijiang [5 ]
Zhang, Kai [4 ]
Guo, Zijian [5 ]
Diao, Jiajie [3 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, Jinan 250101, Shandong, Peoples R China
[2] Shandong Acad Pharmaceut Sci, Key Lab Biopharmaceut, Engn Lab Polysaccharide Drugs, Natl Local Joint Engn Lab Polysaccharide Drugs, Jinan 250101, Shandong, Peoples R China
[3] Univ Cincinnati, Dept Canc Biol, Coll Med, Cincinnati, OH 45267 USA
[4] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA
[5] Nanjing Univ, Sch Chem & Chem Engn, Inst Coordinat Chem, State Key Lab Coordinat Chem, Nanjing 210093, Jiangsu, Peoples R China
基金
美国国家卫生研究院;
关键词
drug screening; mitochondria; lysosome; mitophagy; structured illumination microscopy; FLUORESCENT-PROBES; INDUCED APOPTOSIS; AUTOPHAGY; DYSFUNCTION; PARKINSONS; MITOPHAGY; MICROSCOPY; DYNAMICS; FISSION;
D O I
10.1007/s12274-019-2331-x
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
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, Cellprofiler, 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.
引用
收藏
页码:1009 / 1015
页数:7
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