Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe  

作　　者：Wei Ren Xichuan Ge Meiqi Li Jing Sun Shiyi Li Shu Gao Chunyan Shan Baoxiang Gao Peng Xi 

机构地区：[1]Department of Biomedical Engineering,National Biomedical Imaging Center,College of Future Technology,Peking University,Beijing 100871,China [2]Key Laboratory of Analytical Science and Technology of Hebei Province,College of Chemistry and Material Science,Hebei University,Baoding 071002,China [3]School of Life Sciences,Peking University,Beijing 100871,China [4]National Center for Protein Sciences,Peking University,Beijing 100871,China

出　　处：《Light(Science & Applications)》2024年第9期1741-1756,共16页光（科学与应用)（英文版）

基　　金：supported by the National Key R&D Program of China(2022YFC3401100);National Natural Science Foundation of China(22177024,62025501,31971376,92150301).

摘　　要：Mitochondria are crucial organelles closely associated with cellular metabolism and function.Mitochondrial DNA(mtDNA)encodes a variety of transcripts and proteins essential for cellular function.However,the interaction between the inner membrane(IM)and mtDNA remains elusive due to the limitations in spatiotemporal resolution offered by conventional microscopy and the absence of suitable in vivo probes specifically targeting the IM.Here,we have developed a novel fluorescence probe called HBmito Crimson,characterized by exceptional photostability,fluorogenicity within lipid membranes,and low saturation power.We successfully achieved over 500 frames of lowpower stimulated emission depletion microscopy(STED)imaging to visualize the IM dynamics,with a spatial resolution of 40 nm.By utilizing dual-color imaging of the IM and mtDNA,it has been uncovered that mtDNA tends to habitat at mitochondrial tips or branch points,exhibiting an overall spatially uniform distribution.Notably,the dynamics of mitochondria are intricately associated with the positioning of mtDNA,and fusion consistently occurs in close proximity to mtDNA to minimize pressure during cristae remodeling.In healthy cells,>66%of the mitochondria are Class III(i.e.,mitochondria>5μm or with>12 cristae),while it dropped to<18%in ferroptosis.Mitochondrial dynamics,orchestrated by cristae remodeling,foster the even distribution of mtDNA.Conversely,in conditions of apoptosis and ferroptosis where the cristae structure is compromised,mtDNA distribution becomes irregular.These findings,achieved with unprecedented spatiotemporal resolution,reveal the intricate interplay between cristae and mtDNA and provide insights into the driving forces behind mtDNA distribution.

关 键 词：METABOLISM SATURATION utilizing 

分 类 号：TH742[机械工程—光学工程]