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

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

doi:10.1038/s41377-024-01463-9

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

Original Articles

- Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe
- Light: Science & Applications Vol. 13, Issue 9, Pages: 1741-1756(2024)
- Affiliations：
  
  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
- Author bio：
  
  Chunyan Shan (chunyanshan@pku.edu.cn)
  Baoxiang Gao (bxgao@hbu.edu.cn)
  Peng Xi (xipeng@pku.edu.cn)
- Funds：
- DOI：10.1038/s41377-024-01463-9
  CLC：
- Published：30 September 2024，
  
  Published Online：24 May 2024，
  
  Received：20 November 2023，
  
  Revised：12 April 2024，
  
  Accepted：20 April 2024
- Accepted：
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Ren, W. et al. Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe. Light: Science & Applications, 13, 1741-1756 (2024).
DOI：

Ren, W. et al. Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe. Light: Science & Applications, 13, 1741-1756 (2024). DOI： 10.1038/s41377-024-01463-9.

摘要

Abstract

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 low-power 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 > 5 μm 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

Keywords

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