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

Nano Research 2020年第8期13卷 2149-2155页

作者： Xintian Shao Qixin Chen Lianting Hu Zhiqi Tian Liuyi Liu Fei Liu Fengshan Wang Peixue Ling Zong-Wan Mao Jiajie Diao Shandong Academy of Pharmaceutical Sciences Key Laboratory of BiopharmaceuticalsEngineering Laboratory of Polysaccharide DrugsNational-Local Joint Engineering Laboratory of Polysaccharide DrugsJinan250101China Department of Cancer Biology University of Cincinnati College of MedicineCincinnatiOH45267USA School of Pharmaceutical Sciences Cheeloo College of MedicineShandong UniversityJinan250012China Xintian Shao Qixin Chenand Lianting Hu contributed equally to this work.Shandong First Medical University&Shandong Academy of Medical SciencesJinan250062China Xintian Shao Qixin Chenand Lianting Hu contributed equally to this work.School of Information ManagementWuhan UniversityWuhan430072China MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of ChemistrySun Yat-Sen UniversityGuangzhou510275China

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.

关键词： mitochondria structured illumination microscopy quantification analyze morphology cristae

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