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Descubrimiento de una alternativa de macroautofagia independiente de Atg5/Atg7
Yuya Nishida1, Satoko Arakawa, Kenji Fujitani
1Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Nature
|October 2, 2009
Resumen
La macroautofagia de los mamíferos, un proceso de degradación celular, puede ocurrir a través de dos vías. Existe una vía alternativa, independiente de Atg5/Atg7, junto con la convencional, crucial para ciertas funciones celulares.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Investigación de la autofagia Investigación de la autofagia.
Sus antecedentes:
- La macroautofagia es un proceso celular fundamental para la degradación de los componentes dañados a través de los autofagosomas/autolisosomas.
- Atg5 y Atg7 son ampliamente considerados genes esenciales para la iniciación y ejecución de la macroautofagia en mamíferos.
Objetivo del estudio:
- Investigar la existencia y las características de la macroautofagia en ausencia de Atg5 o Atg7.
- Identificar mecanismos alternativos de formación y degradación de los autofagosomas.
Principales métodos:
- Células de ratón utilizadas que carecen de Atg5 o Atg7.
- Se analizó la formación de autofagosomas/autolisosomas y la degradación de proteínas bajo condiciones de estrés.
- Investigó el papel de proteínas específicas relacionadas con la autofagia (Ulk1, beclin 1) y Rab9.
- Examinó la macroautofagia en tejidos embrionarios in vivo.
Principales resultados:
- Las células de ratón que carecen de Atg5 o Atg7 todavía pueden realizar macroautofagia y degradar proteínas.
- La formación de autofagosomas en esta vía alternativa es independiente de la lipidación LC3 (LC3-II).
- La vía independiente de Atg5/Atg7 involucra a Ulk1, beclin 1 y la fusión vesicular dependiente de Rab9 de los endosomas trans-Golgi y finales.
- Esta vía alternativa se observó en tejidos embrionarios e involucrada en el aclaramiento mitocondrial durante la maduración de los eritroides.
Conclusiones:
- La macroautofagia de los mamíferos se desarrolla a través de al menos dos vías distintas: una vía convencional Atg5/Atg7-dependiente y otra alternativa Atg5/Atg7-independiente.
- El descubrimiento de una vía alternativa amplía nuestra comprensión de los mecanismos de degradación celular y su regulación.
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