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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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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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Abstract

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.