Key result
S6K1 is essential for maintaining muscle structure and force production during hypertrophy, as its absence leads to compromised ribosome biogenesis and p62-positive protein aggregates.
S6K1 is crucial for maintaining skeletal muscle function and structure during hypertrophy, despite not being required for muscle growth itself.
Does not yet alter clinical muscle care; leaves open S6K1 as a research target in hypertrophy.
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.
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Marabita et al. (2016) studied Skeletal muscle hypertrophy. S6K1 deletion / mTOR signaling inhibition was evaluated on Muscle structure and force production. S6K1 is essential for maintaining muscle structure and force production during hypertrophy, as its absence leads to compromised ribosome biogenesis and p62-positive protein aggregates.
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