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Nano Research

Article Title

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

Authors

Xintian Shao, 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
Qixin Chen, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
Lianting Hu, School of Information Management, Wuhan University, Wuhan 430072, China
Zhiqi Tian, Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Liuyi Liu, MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China
Fei Liu, 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 School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Fengshan Wang, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Peixue Ling, 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 School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Zong-Wan Mao, MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China
Jiajie Diao, Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

Keywords

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

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.

Graphical Abstract

Publisher

Tsinghua University Press

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