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Regulación diferencial de distintos complejos Vps34 por AMPK en el estrés nutricional y la autofagia
Joungmok Kim1, Young Chul Kim, Chong Fang
1Department of Oral Biochemistry and Molecular Biology, Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
Cell
|January 22, 2013
Resumen
La proteína quinasa activada por AMP (AMPK) regula diferencialmente los complejos Vps34 durante el estrés nutricional. AMPK inhibe la no-autofagia Vps34 mientras activa los complejos pro-autofagia, controlando la supervivencia celular y la inducción de la autofagia.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La autofagia es una respuesta al estrés celular crucial para la supervivencia durante el hambre de nutrientes.
- La fosfatidilinositol-3 quinasa de clase III, Vps34, es central para el tráfico de vesículas y la inducción de la autofagia, que existe en múltiples complejos proteicos.
- La proteína quinasa activada por AMP (AMPK) es un sensor de energía celular clave involucrado en la regulación metabólica.
Objetivo del estudio:
- Para aclarar el papel de AMPK en la regulación de distintos complejos Vps34.
- Para entender cómo AMPK modula la actividad de Vps34 en respuesta al estrés nutricional.
- Para investigar la interacción entre los complejos AMPK, Vps34 y la inducción de la autofagia.
Principales métodos:
- Análisis del sitio de fosforilación de Vps34 y Beclin1.
- Investigación de la formación y actividad del complejo Vps34.
- Ensayos de respuesta celular bajo condiciones de inanición de glucosa.
Principales resultados:
- AMPK fosforila Vps34 en T163/S165, inhibiendo la actividad no autofágica de Vps34 y la producción de PI(3) P, protegiendo así las células durante la inanición.
- AMPK fosforila Beclin1 en S91/S94, activando el complejo pro-autofagia Vps34 e induciendo la autofagia.
- Atg14L, un componente del complejo proautófago, mejora selectivamente la fosforilación de Beclin1 por AMPK mientras inhibe la fosforilación de Vps34, dirigiendo así los efectos reguladores de AMPK.
Conclusiones:
- La AMPK juega un papel crítico y dual en la regulación de los complejos Vps34 durante el estrés nutricional.
- La fosforilación diferencial de Vps34 y Beclin1 por AMPK dicta el destino celular entre la supervivencia y la autofagia.
- Atg14L actúa como un determinante crucial para la activación o inhibición específica de los complejos Vps34 por AMPK, revelando una intrincada red reguladora.
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