Caged AG10: new tools for spatially predefined mitochondrial uncoupling.
Mol Biosyst
; 5(5): 450-7, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-19381360
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 (DeltaPsi(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 (1)H 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 DeltaPsi(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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Desacopladores
/
Potencial de la Membrana Mitocondrial
/
Anisoles
/
Mitocondrias
/
Nitrilos
Límite:
Animals
Idioma:
En
Revista:
Mol Biosyst
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2009
Tipo del documento:
Article
Pais de publicación:
Reino Unido