VDAC2 inhibe la activación de BAK y la apoptosis mitocondrial
Emily H Y Cheng1, Tatiana V Sheiko, Jill K Fisher
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|July 26, 2003
Resumen
La proteína de la membrana externa mitocondrial VDAC2 secuestra la proteína proapoptótica BAK en un estado inactivo. El desplazamiento de VDAC2 activa BAK, iniciando la apoptosis, revelando un regulador clave de la muerte celular programada.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La vía mitocondrial de la apoptosis es iniciada por las proteínas proapoptóticas BAK y BAX.
- Actualmente se desconoce el mecanismo por el cual las células mantienen BAK en un estado monomérico inactivo en las mitocondrias.
Objetivo del estudio:
- Para dilucidar el mecanismo que regula la conformación inactiva de BAK en las mitocondrias.
- Para identificar las proteínas que interactúan y controlan la actividad de BAK.
Principales métodos:
- Los ensayos de coinmunoprecipitación identifican las proteínas que interactúan con el BAK.
- Análisis de la oligomerización de BAK y la susceptibilidad apoptótica en células deficientes en VDAC2.
- Estudios de sobreexpresión de VDAC2 para evaluar su efecto sobre la activación de BAK y la apoptosis.
Principales resultados:
- Se encontró que BAK estaba complejo con VDAC2, una proteína de la membrana externa mitocondrial de baja abundancia, en células viables.
- VDAC2 interactúa específicamente con la conformación inactiva de BAK.
- Las células deficientes en VDAC2 mostraron un aumento de la oligomerización de BAK y la susceptibilidad a la apoptosis, a diferencia de las células deficientes en VDAC1.
- La sobreexpresión de VDAC2 inhibió la activación de BAK y la vía apoptótica mitocondrial.
Conclusiones:
- VDAC2 actúa como un regulador crítico de la actividad de BAK, manteniéndola en un estado inactivo.
- La activación de la apoptosis implica que las proteínas BH3-only desplacen VDAC2 de BAK, lo que lleva a la homooligomerización de BAK.
- VDAC2 proporciona un vínculo entre la función mitocondrial y la maquinaria apoptótica del núcleo.
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