Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1.
Science
; 380(6652): 1372-1380, 2023 06 30.
Article
em En
| MEDLINE
| ID: mdl-37384704
ABSTRACT
Adenosine monophosphate-activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser415 to suppress energy stress-induced cell death. Inhibiting pS415-RIPK1 by Ampk deficiency or RIPK1 S415A mutation promoted RIPK1 activation. Furthermore, genetic inactivation of RIPK1 protected against ischemic injury in myeloid Ampkα1-deficient mice. Our studies reveal that AMPK phosphorylation of RIPK1 represents a crucial metabolic checkpoint, which dictates cell fate response to metabolic stress, and highlight a previously unappreciated role for the AMPK-RIPK1 axis in integrating metabolism, cell death, and inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Metabolismo Energético
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Proteína Serina-Treonina Quinases de Interação com Receptores
/
Proteínas Quinases Ativadas por AMP
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Necroptose
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos