S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase.
Cell Metab
; 5(6): 476-87, 2007 Jun.
Article
en En
| MEDLINE
| ID: mdl-17550782
ABSTRACT
S6 kinase (S6K) deletion in metazoans causes small cell size, insulin hypersensitivity, and metabolic adaptations; however, the underlying molecular mechanisms are unclear. Here we show that S6K-deficient skeletal muscle cells have increased AMP and inorganic phosphate levels relative to ATP and phosphocreatine, causing AMP-activated protein kinase (AMPK) upregulation. Energy stress and muscle cell atrophy are specifically triggered by the S6K1 deletion, independent of S6K2 activity. Two known AMPK-dependent functions, mitochondrial biogenesis and fatty acid beta-oxidation, are upregulated in S6K-deficient muscle cells, leading to a sharp depletion of lipid content, while glycogen stores are spared. Strikingly, AMPK inhibition in S6K-deficient cells restores cell growth and sensitivity to nutrient signals. These data indicate that S6K1 controls the energy state of the cell and the AMPK-dependent metabolic program, providing a mechanism for cell mass accumulation under high-calorie diet.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adaptación Fisiológica
/
Adenilato Quinasa
/
Eliminación de Gen
/
Músculo Esquelético
/
Proteína S6 Ribosómica
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia