S6 Kinase Deletion Suppresses Muscle Growth Adaptations to Nutrient Availability by Activating AMP Kinase

Victor Aguilar, Samira Alliouachene, Athanassia Sotiropoulos, Andrew Sobering, Yoni Athea, Fatima Djouadi, Sylvain Miraux, Eric Thiaudière, Marc Foretz, Benoit Viollet, Philippe Diolez, Jean Bastin, Paule Benit, Pierre Rustin, David Carling, Marco Sandri, Renée Ventura-Clapier, Mario Pende

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

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 β-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.

Original languageEnglish (US)
Pages (from-to)476-487
Number of pages12
JournalCell Metabolism
Volume5
Issue number6
DOIs
StatePublished - Jun 6 2007
Externally publishedYes

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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