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Caged AG10: new tools for spatially predefined mitochondrial uncoupling

Avionitis, N. and Chalmers, S. and McDougall, C. and Stanton-Humphreys, M.N. and Brown, C.T.A. and McCarron, J.G. and Conway, S.J. (2009) Caged AG10: new tools for spatially predefined mitochondrial uncoupling. Molecular BioSystems, 5. pp. 450-457. ISSN 1742-206X

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The study of mitochondria and mitochondrial Ca2+ signalling in localised regions is hampered by the lack of tools that can uncouple the mitochondrial membrane potential (m) in a spatially predefined manner. Although there are a number of existing mitochondrial uncouplers, these compounds are necessarily membrane permeant and therefore exert their actions in a spatially unselective manner. Herein, we report the synthesis of the first caged (photolabile protected) mitochondrial uncouplers, based on the tyrphostin AG10. We have analysed the laser photolysis of these compounds, using 1H NMR and HPLC, and demonstrate that the major product of caged AG10 photolysis is AG10. It is shown that photolysis within single smooth muscle cells causes a collapse of m consistent with photorelease of AG10. Furthermore, the effect of the photoreleased AG10 is localised to a subcellular region proximal to the site of photolysis, demonstrating for the first time spatially predefined mitochondrial uncoupling.

Item type: Article
ID code: 12988
Keywords: mitochondrial uncoupling, mitochondria, mitochondrial Ca2+, pharmacology, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Molecular Biology, Biotechnology
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Ms Ann Barker-Myles
Date Deposited: 31 Aug 2009 13:35
Last modified: 21 May 2015 11:06

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