Caged AG10: new tools for spatially predefined mitochondrial uncoupling

N. Avionitis, S. Chalmers, C. McDougall, M.N. Stanton-Humphreys, C.T.A. Brown, J.G. McCarron, S.J. Conway

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.
LanguageEnglish
Pages450-457
Number of pages7
JournalMolecular BioSystems
Volume5
DOIs
Publication statusPublished - 2009

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Photolysis
Tyrphostins
Mitochondrial Membrane Potential
Smooth Muscle Myocytes
Mitochondria
Lasers
High Pressure Liquid Chromatography
Membranes

Keywords

  • mitochondrial uncoupling
  • mitochondria
  • mitochondrial Ca2+
  • pharmacology

Cite this

Avionitis, N., Chalmers, S., McDougall, C., Stanton-Humphreys, M. N., Brown, C. T. A., McCarron, J. G., & Conway, S. J. (2009). Caged AG10: new tools for spatially predefined mitochondrial uncoupling. Molecular BioSystems, 5, 450-457. https://doi.org/10.1039/b820415m
Avionitis, N. ; Chalmers, S. ; McDougall, C. ; Stanton-Humphreys, M.N. ; Brown, C.T.A. ; McCarron, J.G. ; Conway, S.J. / Caged AG10: new tools for spatially predefined mitochondrial uncoupling. In: Molecular BioSystems. 2009 ; Vol. 5. pp. 450-457.
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Avionitis, N, Chalmers, S, McDougall, C, Stanton-Humphreys, MN, Brown, CTA, McCarron, JG & Conway, SJ 2009, 'Caged AG10: new tools for spatially predefined mitochondrial uncoupling' Molecular BioSystems, vol. 5, pp. 450-457. https://doi.org/10.1039/b820415m

Caged AG10: new tools for spatially predefined mitochondrial uncoupling. / Avionitis, N.; Chalmers, S.; McDougall, C.; Stanton-Humphreys, M.N.; Brown, C.T.A.; McCarron, J.G.; Conway, S.J.

In: Molecular BioSystems, Vol. 5, 2009, p. 450-457.

Research output: Contribution to journalArticle

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AU - Avionitis, N.

AU - Chalmers, S.

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AU - McCarron, J.G.

AU - Conway, S.J.

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