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

Affiliation

Zhu T(1), Yang G(2), Liu X(3), Xiang P(3), Yang Z(4), Zhang S(2), Chen J(2), Wang H(2), Campos de Souza S(5), Zhang Z(6), Zhang R(2), Tian Y(2), Wu J(2), Tian X(7).
Author information:
(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: [Email]

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.