近日，北京大学未来科技学院的席鹏&单春艳及其研究小组与河北大学的高保祥等人合作并取得一项新进展。经过不懈努力，他们使用低饱和功率探针并通过STED纳米显微镜，实现了嵴和mtDNA相互作用的可视化。相关研究成果已于2024年5月24日在国际知名学术期刊《光：科学与应用》上发表。

据悉，线粒体是与细胞代谢和功能密切相关的重要细胞器。线粒体DNA (mtDNA)编码多种转录本和细胞功能所必需的蛋白质。然而，由于传统显微镜提供的时空分辨率的限制以及缺乏专门针对内膜(IM)的合适的体内探针，内膜(IM)和mtDNA之间的相互作用仍然难以捉摸。

该研究团队开发了一种名为HBmito Crimson的新型荧光探针，其特点是具有优异的光稳定性，脂质膜内的荧光原性和低饱和功率。研究人员成功地实现了超过500帧的低功率受激发射耗尽显微镜(STED)成像，以40nm的空间分辨率可视化IM动力学。研究人员利用IM和mtDNA的双色成像发现，mtDNA倾向于栖息在线粒体尖端或分支点，总体上呈现均匀的空间分布。

值得注意的是，线粒体的动力学与mtDNA的定位有着复杂的关系，融合总是发生在靠近mtDNA的地方，以减少嵴重塑过程中的压力。在健康细胞中，>66%的线粒体为III类(即>5 μm或具有>12个嵴的线粒体)，而在铁死亡细胞中，这一比例降至<18%。通过嵴重塑，线粒体动力学促进了线粒体dna的均匀分布。相反，在细胞凋亡和铁死亡的条件下，嵴结构受损，mtDNA分布变得不规则。这些发现以前所未有的时空分辨率实现，揭示了嵴和mtDNA之间复杂的相互作用，并为mtDNA分布背后的驱动力提供了见解。

附：英文原文

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

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

Issue&Volume: 2024-05-24

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 40nm. 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.

DOI: 10.1038/s41377-024-01463-9

Source: https://www.nature.com/articles/s41377-024-01463-9