Specific detection of intramitochondrial superoxide produced by either cell activation or apoptosis by employing a newly developed cell-permeative lucigenin derivative, 10,10′-dimethyl-9,9′-biacridinium bis(monomethyl terephthalate) |
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| Institution: | 1. Division of Molecular Medicine Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan;2. Division of Chemistry, Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan;1. College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, China;2. State Key Laboratory of Fine Chemicals, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;3. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China;1. National Institute for Food and Drug Control, Institute of Chemical Drug Control, TianTan XiLi 2, Beijing 100050, China;2. College of Chemistry, Beijing Normal University, Xinjiekouwai Street 19, Beijing 100875, China;3. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China;1. Department of Chemistry, University of Science and Technology of China, Hefei, 230026, PR China;2. School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China;1. CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Research Centre for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China;2. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China;3. University of Chinese Academy of Sciences, Beijing, 100049, China;1. Molecular Bioenergetics Group, Goethe-University, D-60590 Frankfurt am Main, Germany;2. Functional Proteomics, SFB815 Core Unit, Medical School, Goethe-University, D-60590 Frankfurt am Main, Germany;3. Cluster of Excellence Frankfurt “Macromolecular Complexes,” Goethe-University, D-60590 Frankfurt am Main, Germany;4. Radboud University Medical Center, Nijmegen Center for Mitochondrial Disorders, 6500 GA Nijmegen, The Netherlands;5. Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital, Frankfurt am Main, Germany |
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| Abstract: | Here we developed a new cell-permeative lucigenin derivative, 10,10′-dimethyl-9,9′-biacridinium bis(monomethyl terephthalate) (MMT), to detect intracellular superoxide production. Both MMT and lucigenin were specific to superoxide among reactive oxygen species tested. Although lucigenin barely penetrated into cells, MMT accumulated in mitochondria in a variety of cells such as neutrophils. By employing MMT, we found that, upon activation of neutrophils with phorbol myristate acetate, superoxide was generated extracellularly as well as intramitochondrially and that such intramitochondrial superoxide production was dependent on oxidative phosphorylation. We also found that, during apoptosis, superoxide was gradually produced in mitochondria in association with phosphatidylserine exposure and that the kinetics of superoxide production was very heterogeneous at the single-cell level. Thus this study demonstrates that MMT could serve as a specific probe for intramitochondrial superoxide in either activated or apoptotic cells. |
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| Keywords: | Mitochondria Superoxide Lucigenin derivative Visualization Oxidative phosphorylation Apoptosis Free radicals |
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