Reference

Proc. Natl. Acad. Sci. U.S.A. 113:13063-13068.46.cover

Authors

Irene Lopez-Fabuel, Juliette Le Douce, Angela Logan, Andrew M. James, Gilles Bonvento, Michael P. Murphy, Angeles Almeida y Juan P. Bolaños

Abstract

Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences and the structural organization of the mitochondrial respiratory chain is unknown. Here, we investigated this issue and found that, in neurons, mitochondrial complex I is predominantly assembled into supercomplexes, whereas in astrocytes the abundance of free complex I is higher. The presence of free complex I in astrocytes correlates with the severalfold higher reactive oxygen species (ROS) production by astrocytes compared with neurons. Using a complexomics approach, we found that the complex I subunit NDUFS1 was more abundant in neurons than in astrocytes. Interestingly, NDUFS1 knockdown in neurons decreased the association of complex I into supercomplexes, leading to impaired oxygen consumption and increased mitochondrial ROS. Conversely, overexpression of NDUFS1 in astrocytes promoted complex I incorporation into supercomplexes, decreasing ROS. Thus, complex I assembly into supercomplexes regulates ROS production and may contribute to the bioenergetic differences between neurons and astrocytes.

Description

En este estudio revelamos que las células neurales difieren en el modo en el que organizan su cadena respiratoria mitocondrial (CRM). Así, el complejo I está principalmente libre en astrocitos, pero unido a supercomplejos en neuronas. Esta diferencia determina una mayor producción de ROS mitocondriales en astrocitos, y una mejor eficiencia en la transferencia electrónica de la CRM en neuronas.

 

grupo bolanos

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de investigación de Juan Pedro Bolaños está interesado en descifrar los mecanismos moleculares responsables del acoplamiento metabólico y redox en las células neurales. Nuestro objetivo a medio y largo plazo es identificar dianas concretas causantes de los desbalances en el metabolismo energético cerebral que se observan en algunas enfermedades neurológicas.

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