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La conjugación de ATG12 con ATG3 regula la homeostasis mitocondrial y la muerte celular

Lilliana Radoshevich¹, Lyndsay Murrow, Nan Chen

¹Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.

|August 21, 2010

Resumen

El complejo ATG12-ATG3 regula la masa mitocondrial y la muerte celular, revelando un nuevo papel para el sistema de conjugación ATG12 más allá de su función en la iniciación de la autofagia.

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
Investigación de la autofagia Investigación de la autofagia.

Sus antecedentes:

ATG12 es un modificador similar a la ubiquitina esencial para la macroautofagia.
Su objetivo de conjugación conocido es ATG5, un regulador de la autofagia.
ATG3 es una enzima tipo E2 crítica para la lipidación de ATG8/LC3 durante la autofagia.

Objetivo del estudio:

Para identificar nuevos sustratos para la conjugación de ATG12.
Para investigar la función de la conjugación de ATG12 con ATG3.3.
Explorar el papel del complejo ATG12-ATG3 en los procesos celulares.

Principales métodos:

Investigó la conjugación de ATG12 con ATG3 utilizando ATG7 como la enzima E1.
Se analizó el impacto de interrumpir la formación del complejo ATG12-ATG3 en la autofagia.
Evaluar los cambios en la masa mitocondrial y las vías de muerte celular.

Principales resultados:

ATG3 identificado como un nuevo sustrato para la conjugación de ATG12, formando un complejo ATG12-ATG3 covalente.
La interrupción de la conjugación de ATG12 con ATG3 no afectó la autofagia inducida por el hambre.
La falta de formación del complejo ATG12-ATG3 condujo a un aumento de la masa mitocondrial e inhibió la muerte celular mitocondrial.

Conclusiones:

El sistema de conjugación ATG12-ATG3 juega un papel en la homeostasis mitocondrial, independientemente de los primeros pasos de la autofagia.
Este hallazgo implica el sistema de conjugación ATG12 en las funciones celulares más allá de la formación del autofagosoma.

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