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Estructura pre-autofagosómica híbrida de mamíferos El HyPAS genera autofagosomas
Suresh Kumar1, Ruheena Javed1, Michal Mudd1
1Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Cell
|November 6, 2021
Resumen
La biogénesis autofagosómica implica un nuevo compartimiento de membrana híbrido, HyPAS, formado a partir de vías de Golgi y endosómicas. Este proceso está dirigido por las proteínas del SARS-CoV-2, lo que afecta la formación de los autofagosomas.
Área de la Ciencia:
- Biología celular
- Biología molecular
- Investigación de la autofagia
Sus antecedentes:
- Los mecanismos precisos que rigen la biogénesis de los autofagosomas de los mamíferos no están completamente aclarados.
- Comprender los orígenes de los autofagosomas es crucial para la salud celular y la investigación de enfermedades.
Objetivo del estudio:
- Definir el origen y la biogénesis de los autofagosomas de los mamíferos.
- Identificar nuevos compartimentos de membrana involucrados en la formación de los autofagosomas.
- Investigar el impacto de los factores virales en el ensamblaje del precursor del autofagosoma.
Principales métodos:
- Se han utilizado ensayos de fusión celular e in vitro.
- Investigó el papel de las vesículas FIP200 y las membranas ATG16L1.
- Se analizó el efecto de la infección por SARS-CoV-2 y la expresión de nsp6.
Principales resultados:
- Se identificó una estructura pre-autofagosómica híbrida (HyPAS) formada por la fusión de vesículas FIP200 derivadas de cis-Golgi y membranas ATG16L1 derivadas endosomalmente.
- Descubrió un nuevo aparato que controla la biogénesis de HyPAS y las membranas precursoras autofagosómicas.
- Se demostró que la formación de HyPAS es inhibida por la infección por SARS-CoV-2 y la expresión de nsp6.
- Se ha demostrado que HyPAS puede ser modulado por agentes farmacológicos.
Conclusiones:
- Las membranas de los autofagosomas de los mamíferos se originan en un compartimento híbrido (HyPAS) que integra las vías secretoras y endosómicas.
- La biogénesis de los autofagosomas es un objetivo para los factores microbianos, ejemplificado por las proteínas del coronavirus.
- Este descubrimiento proporciona nuevos conocimientos sobre la regulación de la autofagia y su manipulación por parte de los virus.
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