Caged AG10: new tools for spatially predefined mitochondrial uncoupling

Nicolaos Avlonitis, Susan Chalmers, Craig McDougall, Megan N. Stanton-Humphreys, C Tom A Brown, John G. McCarron, Stuart J. Conway

Research output: Contribution to journalArticlepeer-review

9 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 (Delta Psi(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 H-1 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 Delta Psi(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.

Original languageEnglish
Pages (from-to)450-457
Number of pages8
JournalMolecular BioSystems
Volume5
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • SMOOTH-MUSCLE
  • L-GLUTAMATE
  • PHOTOLABILE CHELATORS
  • PHOTODYNAMIC THERAPY
  • INOSITOL PHOSPHATES
  • DIVALENT-CATIONS
  • CARBOXYLIC-ACIDS
  • ION CHANNELS
  • PHOTORELEASE
  • CALCIUM

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