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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
Published on: April 1, 2011
El PARL romboide mitocondrial regula la liberación del citocromo c durante la apoptosis a través de la remodelación
Sara Cipolat1, Tomasz Rudka, Dieter Hartmann
1Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.
Cell
|July 15, 2006
Resumen
La proteína parecida al romboide asociada a la presenilina (PARL) es esencial para el procesamiento de OPA1, una proteína mitocondrial crucial para prevenir la apoptosis. La deficiencia de PARL conduce a la atrofia multisistémico y la muerte en ratones debido al aumento de la muerte celular programada.
Área de la Ciencia:
- Biología mitocondrial Biología mitocondrial
- La apoptosis celular es una apoptosis celular.
- La función de la proteasa es la función de la proteasa.
Sus antecedentes:
- Los romboides son proteasas de membrana integradas que participan en la señalización.
- El tipo romboide asociado a la presenilina (PARL) es un romboide mitocondrial con una función desconocida.
- El ortólogo de levadura de PARL está implicado en la fusión mitocondrial.
Objetivo del estudio:
- Para investigar la función de los romboides asociados a la presenilina (PARL) en los mamíferos.
- Para determinar el papel de PARL en la función mitocondrial y la apoptosis.
- Para dilucidar el mecanismo por el cual PARL influye en la muerte celular.
Principales métodos:
- Generación y análisis de Parl-/- ratones.
- Evaluación de la apoptosis en células y tejidos Parl-/- .
- Ensayos de morfología y función mitocondrial.
- Análisis del procesamiento y localización de OPA1.
- Estudios complementarios con OPA1 dirigidos al espacio intermembranar.
Principales resultados:
- Los ratones parl-/- exhiben una atrofia multisistémico progresiva y muerte caquéctica después del desarrollo.
- Se observa un aumento de la apoptosis en las células y tejidos Parl-/- , tanto in vitro como ex vivo.
- Las células parl-/- no están protegidas contra estímulos apoptóticos intrínsecos debido al deterioro de la función OPA1.
- Reducción de los niveles de OPA1 soluble en el espacio intermembranar de las mitocondrias Parl-/-.
- PARL es crucial para el procesamiento de OPA1 y la orientación del espacio intermembranar.
- Las mitocondrias parl-/- muestran una remodelación acelerada de las cristales y la liberación del citocromo c durante la apoptosis.
Conclusiones:
- PARL juega un papel crítico en la regulación de la apoptosis mediante el control del procesamiento de OPA1.
- La proteólisis intramembrana regulada, mediada por PARL, es un factor clave en el control de la apoptosis.
- La deficiencia de PARL conduce a una disfunción mitocondrial y una mayor susceptibilidad a la muerte celular apoptótica.
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