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Mecanismo del desacoplamiento UCP1 dependiente de ácidos grasos en las mitocondrias de grasa marrón

Andriy Fedorenko¹, Polina V Lishko, Yuriy Kirichok

¹Department of Physiology, University of California San Francisco, UCSF Mail Code 2140, Genentech Hall Room N272F, 600 16th Street, San Francisco, CA 94158, USA.

|October 16, 2012

Resumen

La proteína de desacoplamiento mitocondrial 1 (UCP1) actúa como un anión de ácido graso / simportador de protones. Este mecanismo permite que las mitocondrias de grasa marrón generen calor en lugar de ATP, regulando la eficiencia metabólica.

Área de la Ciencia:

Fisiología mitocondrial fisiología mitocondrial.
La bioquímica es la bioquímica.
El metabolismo celular es el metabolismo celular.

Sus antecedentes:

La proteína de desacoplamiento mitocondrial 1 (UCP1) impulsa la termogénesis sin cifrado en el tejido adiposo marrón (BAT).
La activación de UCP1 por ácidos grasos de cadena larga (LCFA) aumenta la conductividad de la membrana mitocondrial interna (MMI), desacoplando la producción de calor de la síntesis de ATP.
El mecanismo preciso del transporte de protones mediado por UCP1 sigue sin resolverse.

Objetivo del estudio:

Para aclarar el mecanismo de transporte de UCP1.1.
Para determinar cómo los LCFAs activan UCP1 para la termogénesis.

Principales métodos:

Se realizaron mediciones directas de las corrientes UCP1 con pinzas de parche en las membranas mitocondriales internas de las mitocondrias de las BAT.
Análisis de la interacción de UCP1 con LCFAs y el transporte de protones.

Principales resultados:

UCP1 funciona como un anión de ácido graso de cadena larga / H ((+) simportador.
Los aniones LCFA permanecen unidos a UCP1 debido a las interacciones hidrofóbicas, lo que permite que UCP1 actúe como un portador de H ((+).
Este mecanismo dependiente del LCFA facilita el transporte de protones transmembrana.

Conclusiones:

La UCP1 funciona como un portador de protones activado por LCFA, crucial para la termogénesis sin torceduras.
Los hallazgos resuelven la pregunta de larga data sobre el mecanismo de transporte de UCP1.
Mecanismos similares pueden regular la eficiencia metabólica en otros tejidos a través de miembros de la familia SLC25.

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