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

doi:10.1016/j.cmet.2007.05.006

S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase

Cell Metab. 2007 Jun;5(6):476-87. doi: 10.1016/j.cmet.2007.05.006.

Authors

Victor Aguilar¹, 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

Affiliation

¹ INSERM, U845, Paris F-75015, France; Université Paris Descartes, UMRS-845, Paris F-75015, France.

PMID: 17550782
DOI: 10.1016/j.cmet.2007.05.006

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological*
Adenylate Kinase / antagonists & inhibitors
Adenylate Kinase / genetics
Adenylate Kinase / metabolism*
Aminoimidazole Carboxamide / analogs & derivatives
Aminoimidazole Carboxamide / metabolism
Animals
Cells, Cultured
Energy Metabolism
Enzyme Activation
Fasting
Gene Deletion*
Glucose Tolerance Test
Green Fluorescent Proteins / metabolism
Hypoglycemic Agents / metabolism
Immunoblotting
Magnetic Resonance Spectroscopy
Mice
Mice, Knockout
Muscle Fibers, Skeletal / physiology
Muscle, Skeletal / physiology*
Palmitates / metabolism
Phosphatidylinositol 3-Kinases / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleotides / metabolism
Ribosomal Protein S6 / physiology*

Substances

Hypoglycemic Agents
Palmitates
RNA, Small Interfering
Ribonucleotides
Ribosomal Protein S6
enhanced green fluorescent protein
ribosomal protein S6, mouse
Green Fluorescent Proteins
Aminoimidazole Carboxamide
Phosphatidylinositol 3-Kinases
Adenylate Kinase
AICA ribonucleotide

Abstract

Publication types

MeSH terms

Substances

Grants and funding