Live cell mitochondrial 3-dimensional dynamic ultrastructures under oxidative phosphorylation revealed by a Pyridine-BODIPY probe

Tong Zhu; Guanqing Yang; Xiaolu Liu; Pan Xiang; Zhenghui Yang; Sijing Zhang; Juan Chen; Hong Wang; Senio Campos de Souza; Zhongping Zhang; Ruilong Zhang; Yupeng Tian; Jieying Wu; Xiaohe Tian

doi:10.1016/j.bios.2021.113036

Live cell mitochondrial 3-dimensional dynamic ultrastructures under oxidative phosphorylation revealed by a Pyridine-BODIPY probe

Biosens Bioelectron. 2021 Apr 15:178:113036. doi: 10.1016/j.bios.2021.113036. Epub 2021 Jan 28.

Authors

Affiliations

¹ Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, 610041, China; School of Life Science, Anhui University, Hefei, 230601, PR China.
² Department of Chemistry, Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Anhui University, Hefei, 230601, PR China.
³ School of Life Science, Anhui University, Hefei, 230601, PR China.
⁴ Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, PR China.
⁵ Department of Chemistry, University College London, London University College London, Gower Street, London, WC1E 6BT, UK.
⁶ Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, PR China; CAS Center for Excellence in Nanoscience, Institute of Intelligent Machines, Chinese Academy of Science, Hefei, China.
⁷ Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, 610041, China; School of Life Science, Anhui University, Hefei, 230601, PR China; Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, PR China; Department of Chemistry, University College London, London University College London, Gower Street, London, WC1E 6BT, UK. Electronic address: xiaohe.t@ahu.edu.cn.

PMID: 33548656
DOI: 10.1016/j.bios.2021.113036

Abstract

Recent advancements in super-resolution nanoscopy allowed the study of mitochondrial biology at nanoscale and boosted the understanding its correlated cellular processes those were previously poorly understood. Nevertheless, studying mitochondrial ultrastructure remains a challenge due to the lack of probes that could target specific mitochondrial substances (e.g. cristae or mtDNA) and survive under harsh super-resolution optical conditions. Herein, in this work, we have rationally constructed a pyridine-BODIPY (Py-BODIPY) derivative that could target mitochondrial membrane in living cells without interfering its physiological microenvironments. Furthermore, we found Py-BODIPY is a membrane potential independent probe, hence it is not limit to live-cell staining but also showed a strong internalization into pre-fixed and stimulus disrupted sample. Importantly, its cristae specificity and superb photostability allow the observation of mitochondrial dynamic nano-structures with an unprecedented resolution, allow demonstrating how mitochondrial 3D ultrastructure evolved under oxidative phosphorylation condition.

Keywords: 3-Dimensional dynamic; BODIPY-Pyridine derivative; Mitochondrial ultrastructure; Oxidative phosphorylation; STED nanoscopy.

MeSH terms

Biosensing Techniques*
Boron Compounds
Humans
Mitochondrial Dynamics*
Oxidative Phosphorylation
Pyridines

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Pyridines