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Nano Research 2020, 13(8): 2149-2155 https://doi.org/10.1007/s12274-020-2822-9
Research Article | Issue | Published: 05 August 2020

Super-resolution quantification of nanoscale damage to mitochondria in live cells

Show Author's Information Xintian Shao1,2,3,§,  Qixin Chen4,§,  Lianting Hu5,§,  Zhiqi Tian2,  Liuyi Liu6,  Fei Liu1,3,  Fengshan Wang3,  Peixue Ling1,3( ),  Zong-Wan Mao6( ),  Jiajie Diao2( )
Shandong Academy of Pharmaceutical Sciences, 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
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
School of Information Management, Wuhan University, Wuhan 430072, China
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China

§ Xintian Shao, Qixin Chen, and Lianting Hu contributed equally to this work.

Keywords:
morphology, mitochondria, structured illumination microscopy, quantification analyze, cristae
Topics:
CytologyDiagnosisMorphology
Cite this article:
Shao X, Chen Q, Hu L, et al. Super-resolution quantification of nanoscale damage to mitochondria in live cells. Nano Research, 2020, 13(8): 2149-2155. https://doi.org/10.1007/s12274-020-2822-9
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Abstract Full text Electronic supplementary material About this article

Mitochondrial damage, characterized by altered morphological distribution and the damage of cristae, is closely associated with mitochondrial disease. However, imaging methods for capturing mitochondrial morphology at the nanoscale level in live samples remain unavailable, which seriously hinders the accurate evaluation and diagnosis of mitochondrial-related diseases. In response, we propose a super-resolution quantification strategy based on structured illumination microscopy (SIM) for the rapid, accurate evaluation of mitochondrial morphology. Using the strategy, we accurately captured the morphological distribution of mitochondria at the nanoscale level in a way generally applicable to checking various cell processes and identifying patients with mitochondrial disease who exhibit the SLC25A46 mutation. We also used algorithm-assisted super-resolution imaging to quantitatively analyze damage to mitochondrial cristae, which supports a novel drug screening strategy—high-resolution drug screening—for investigating drugs’ pharmacodynamics on organelles in living cells. In short, our strategy improves the accurate examination of changes in mitochondrial morphology in living cells and indicates new ways in which SIM-imaging can assist in diagnosing mitochondrial disease at the single-cell level.


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Abstract
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Electronic supplementary material
About this article

Super-resolution quantification of nanoscale damage to mitochondria in live cells

Show Author's information Xintian Shao1,2,3,§, Qixin Chen4,§, Lianting Hu5,§, Zhiqi Tian2, Liuyi Liu6, Fei Liu1,3, Fengshan Wang3, Peixue Ling1,3( ), Zong-Wan Mao6( ), Jiajie Diao2( )
Shandong Academy of Pharmaceutical Sciences, 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
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
School of Information Management, Wuhan University, Wuhan 430072, China
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China

§ Xintian Shao, Qixin Chen, and Lianting Hu contributed equally to this work.

Abstract

Mitochondrial damage, characterized by altered morphological distribution and the damage of cristae, is closely associated with mitochondrial disease. However, imaging methods for capturing mitochondrial morphology at the nanoscale level in live samples remain unavailable, which seriously hinders the accurate evaluation and diagnosis of mitochondrial-related diseases. In response, we propose a super-resolution quantification strategy based on structured illumination microscopy (SIM) for the rapid, accurate evaluation of mitochondrial morphology. Using the strategy, we accurately captured the morphological distribution of mitochondria at the nanoscale level in a way generally applicable to checking various cell processes and identifying patients with mitochondrial disease who exhibit the SLC25A46 mutation. We also used algorithm-assisted super-resolution imaging to quantitatively analyze damage to mitochondrial cristae, which supports a novel drug screening strategy—high-resolution drug screening—for investigating drugs’ pharmacodynamics on organelles in living cells. In short, our strategy improves the accurate examination of changes in mitochondrial morphology in living cells and indicates new ways in which SIM-imaging can assist in diagnosing mitochondrial disease at the single-cell level.

Keywords: morphology, mitochondria, structured illumination microscopy, quantification analyze, cristae

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Publication history
Copyright
Acknowledgements

Publication history

Received: 26 March 2020
Revised: 17 April 2020
Accepted: 18 April 2020
Published: 05 August 2020
Issue date: August 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the Special Project for the Shandong Provincial Key Laboratory (No. SDKL2017023), the National key R&D Plan Key Research Projects of Modernization of Traditional Chinese Medicine (No. 2019 YFC1711203) and Shandong Provincial Enterprise Project for Talents Development to P. X. L., Key Research and Development Plan of Shandong Province (Nos. 2018GSF121033, 2019GSF108225, and 2019JZZY010520) and Outstanding Contribution to the Shandong Middle-aged and Young Experts to F. L., Academic promotion program of Shandong First Medical University (No. 2019LJ003) to Q. X. C. We also thank Dr. Taosheng Huang for kindly gifted SLC25A46 normal and mutant cell line.

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