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

Qixin Chen, Xintian Shao, Zhiqi Tian, Yang Chen, Payel Mondal, Fei Liu, Fengshan Wang, Peixue Ling, Weijiang He, Kai Zhang, Zijian Guo, Jiajie Diao

Research output: Contribution to journalArticle

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, 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. [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalNano Research
DOIs
StatePublished - Jan 1 2019

Keywords

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

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

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  • Cite this

    Chen, Q., Shao, X., Tian, Z., Chen, Y., Mondal, P., Liu, F., Wang, F., Ling, P., He, W., Zhang, K., Guo, Z., & Diao, J. (2019). Nanoscale monitoring of mitochondria and lysosome interactions for drug screening and discovery. Nano Research. https://doi.org/10.1007/s12274-019-2331-x