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Una vía coordinada por DELE1 transmite el estrés mitocondrial al citosol

Evelyn Fessler¹, Eva-Maria Eckl¹, Sabine Schmitt²

¹Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.

|March 6, 2020

Resumen

Los científicos descubrieron una nueva vía que vincula el estrés mitocondrial con la respuesta integrada al estrés de la célula. Esta vía involucra a la proteasa mitocondrial OMA1 y la proteína DELE1, que activan la quinasa HRI, crucial para la homeostasis celular.

Área de la Ciencia:

Biología celular
Biología mitocondrial
Señalización de la respuesta al estrés

Sus antecedentes:

La disfunción mitocondrial afecta la homeostasis celular y está implicada en el envejecimiento y la enfermedad.
Las señales de estrés mitocondrial deben comunicarse al citosol para activar la respuesta integrada al estrés (ISR).
Se desconoce el mecanismo molecular específico que vincula la perturbación mitocondrial con la activación de la ISR.

Objetivo del estudio:

Identificar los componentes moleculares responsables de transmitir las señales de estrés mitocondrial al citosol.
Para aclarar la vía que desencadena la respuesta al estrés integrado (ISR) sobre el daño mitocondrial.

Principales métodos:

Utilizó la ingeniería genómica y la genética haploide para una selección imparcial.
Centrado en la identificación de genes que influyen en la inducción de la proteína homóloga C/EBP (CHOP), un mediador clave de la ISR.

Principales resultados:

Se identificaron OMA1 (proteasa mitocondrial) y DELE1 como componentes clave de la vía de respuesta al estrés mitocondrial.
Se demostró que la activación de OMA1 conduce a la escisión de DELE1, generando una forma citosólica que activa la HRI quinasa.
Este eje OMA1-DELE1-HRI constituye el eslabón perdido en la señalización de estrés mitocondrial a la ISR.

Conclusiones:

La vía OMA1-DELE1-HRI es un mediador crítico del estrés mitocondrial.
Comprender esta vía ofrece objetivos terapéuticos potenciales para enfermedades que involucran disfunción mitocondrial.
La modulación de esta vía podría ser una estrategia para manejar las respuestas celulares al daño mitocondrial.

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