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Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
Published on: September 7, 2012
El translocator ADP/ATP no es esencial para el poro de transición de permeabilidad mitocondrial
Jason E Kokoszka1, Katrina G Waymire, Shawn E Levy
1Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, California 92697, USA.
Nature
|January 30, 2004
Resumen
Los translocatores de nucleótidos de adenina (ANT) no son esenciales para la formación del poro de transición de permeabilidad mitocondrial (mtPTP) durante la apoptosis. Si bien las ANT regulan la activación de mtPTP, su ausencia no impide la señalización de la muerte celular.
Área de la Ciencia:
- Biología mitocondrial Biología mitocondrial
- Las vías de la muerte celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El poro de transición de permeabilidad mitocondrial (mtPTP) es central para la apoptosis.
- Los translocatores de nucleótidos de adenina (ANT) son componentes de la mtPTP, que intercambian ATP por ADP.
- Las ANT están potencialmente involucradas en la regulación de la muerte celular.
Objetivo del estudio:
- Investigar el papel de las ANT en la formación y función de mtPTP.
- Para determinar si las ANT son esenciales para la apoptosis mediada por mtPTP.
Principales métodos:
- La inactivación genética de las isoformas de ANT en el hígado de ratón.
- Análisis de la activación de mtPTP en mitocondrias aisladas.
- Evaluación de la inducción de la muerte celular en los hepatocitos.
Principales resultados:
- Las mitocondrias que carecen de ANT aún podrían someterse a una transición de permeabilidad y liberar citocromo c.
- Se requirió un aumento de Ca2+ para la activación de mtPTP en las mitocondrias deficientes en ANT.
- Los ligandos ANT ya no podían regular el mtPTP en su ausencia.
- Los hepatocitos que carecían de ANT seguían siendo sensibles a los inductores de la muerte celular.
Conclusiones:
- Las ANT son componentes estructurales no esenciales del mtPTP.
- Las ANT desempeñan un papel regulador en la activación y función de mtPTP.
- La ausencia de ANT no abole el proceso apoptótico.
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