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Coordinación neuroendocrina de la señalización de estrés mitocondrial y la proteostasis

Kristen M Berendzen¹, Jenni Durieux¹, Li-Wa Shao²

¹The Glenn Center for Aging Research, Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

|September 10, 2016

Resumen

Las enfermedades neurodegenerativas causan cambios metabólicos generalizados. Este estudio revela que las señales de estrés neuronal, propagadas por la serotonina, inducen una respuesta mitocondrial que afecta a la fisiología de todo el animal.

Área de la Ciencia:

Neurobiología
Biología celular
Regulación del metabolismo

Sus antecedentes:

Las enfermedades neurodegenerativas implican agregados proteicos tóxicos y alteraciones metabólicas sistémicas.
El mecanismo que vincula el estrés del sistema nervioso central con los cambios metabólicos periféricos no está claro.
El estrés proteotóxico en las neuronas puede desencadenar respuestas sistémicas a través de la señalización endocrina.

Objetivo del estudio:

Investigar el papel del estrés neuronal en la regulación de la homeostasis mitocondrial durante la enfermedad proteotóxica.
Elucidar las vías de señalización involucradas en la respuesta sistémica a la proteotoxicidad neuronal.

Principales métodos:

Se utilizó C. elegans como organismo modelo para estudiar la agregación de proteínas y el estrés neuronal.
Investigó la interacción de las proteínas propensas a la agregación con las mitocondrias.
Se evaluó la inducción de la respuesta de la proteína desplegada mitocondrial (UPR ((mt)).
Se examinó el papel de la liberación de vesículas del núcleo denso y la secreción de serotonina en la propagación de la señal.

Principales resultados:

Una proteína propensa a la agregación en las neuronas se une a las mitocondrias, induciendo una UPR global.
Esta respuesta mitocondrial afecta a toda la fisiología animal.
La secreción de serotonina es esencial para la propagación de la señal de estrés.
Los hallazgos sugieren que una red de detección de nutrientes es cooptada para la comunicación interorganal.

Conclusiones:

El estrés proteotóxico neuronal puede inducir cambios metabólicos sistémicos a través de la UPR.
La señalización mediada por la serotonina es crucial para comunicar el estrés mitocondrial de las neuronas.
Este mecanismo destaca una nueva vía para la comunicación de célula a célula en respuesta al estrés de plegamiento de proteínas.

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