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Las chaperonas del receptor sigma-1 en la interfaz ER-mitocondria regulan la señalización Ca2+ y la supervivencia
1Cellular Pathobiology Unit, Plasticity and Development Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, MD 21224, USA. thayashi@intra.nida.nih.gov
Cell
|November 6, 2007
Resumen
El receptor sigma-1 (Sig-1R) en la interfaz ER-mitocondría regula la señalización del calcio. La disociación de Sig-1R de BiP mejora la absorción de calcio mitocondrial, lo que afecta la supervivencia celular y la respuesta al estrés ER.
Área de la Ciencia:
- Biología celular Biología celular.
- La función mitocondrial es la función mitocondrial.
- Dinámica del retículo endoplasmático Dinámica del retículo endoplasmático
Sus antecedentes:
- La comunicación entre el retículo endoplasmático (ER) y las mitocondrias es vital para la producción de energía celular y la supervivencia.
- La membrana ER asociada a las mitocondrias (MAM) facilita la transferencia directa de calcio (Ca2+) desde la ER a las mitocondrias a través de los receptores de inositol 1,4,5-trisfosfato (IP3R).
Objetivo del estudio:
- Para investigar el papel del receptor sigma-1 de la proteína ER (Sig-1R) como regulador de la comunicación ER-mitocondrial.
- Para aclarar el mecanismo por el cual Sig-1R modula la señalización de calcio en el MAM.
Principales métodos:
- Caracterización de Sig-1R como un chaperón receptor sensible a Ca2+ y operado por ligandos en el MAM.
- Análisis de la formación del complejo Sig-1R con BiP bajo diferentes condiciones de ER Ca2+.
- Evaluación de la translocación de Sig-1R bajo estrés ER crónico.
- Evaluación del impacto de los niveles de Sig-1R en la respuesta al estrés ER y la apoptosis.
Principales resultados:
- Sig-1R funciona como un chaperón sensible al Ca2+ y operado por ligandos en el MAM.
- Sig-1R normalmente tiene complejos con BiP en el MAM; la disociación ocurre con el agotamiento de ER Ca2+ o la estimulación del ligando.
- La disociación de Sig-1R prolonga la señalización de Ca2+ hacia las mitocondrias a través de las IP3R.
- Sig-1R puede traslocarse durante el estrés ER crónico, y sus niveles influyen en el destino celular (contrarrestar el estrés o mejorar la apoptosis).
Conclusiones:
- La maquinaria de acompañamiento de ER en el MAM, que involucra a Sig-1R, detecta los niveles de Ca2+ de ER.
- Este mecanismo de detección regula la señalización ER-mitocondrial de Ca2+ y, en última instancia, la supervivencia celular.
- Sig-1R juega un papel crítico en el mantenimiento de la homeostasis celular bajo estrés mediante la modulación de la comunicación interorganellar.
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