S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy

Manuela Marabita, Martina Baraldo, Francesca Solagna, Judith Johanna Maria Ceelen, Roberta Sartori, Hendrik Nolte, Ivan Nemazanyy, Stéphane Pyronnet, Marcus Kruger, Mario Pende, Bert Blaauw

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Loss of skeletal muscle mass and force aggravates age-related sarcopenia and numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a major role in stimulating adult muscle growth; however, the functional role of its downstream mediators in vivo is unknown. Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its sensitivity to rapamycin. However, we report that, while not required for muscle growth, S6K1 is essential for maintaining muscle structure and force production. Hypertrophy in the absence of S6K1 is characterized by compromised ribosome biogenesis and the formation of p62-positive protein aggregates. These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy.

Original languageEnglish
Pages (from-to)501-513
Number of pages13
JournalCell Reports
Issue number2
StatePublished - 4 Oct 2016
Externally publishedYes


  • AKT
  • S6K1
  • hypertrophy
  • mTOR
  • muscle force
  • p62
  • protein aggregates
  • rapamycin
  • skeletal muscle


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