Figure 9. Scheme representing the effects of the early stages of disuse on gastrocnemius muscle.

Skeletal muscle disuse would cause down-regulation of pro-fusion proteins leading to mitochondrial dysfunction and AMPK activation. AMPK activation leads to the activation of FoxO, which induces the transcription of genes encoding proteins involved in protein degradation via both the autophagy and the ubiquitin proteasome pathways. The increase in the rate of protein degradation causes gastrocnemius atrophy. AMPK might also prevent the down-regulation of PGC-1α in gastrocnemius in the early stages of HU. Changes of protein synthesis would not be responsible for gastrocnemius atrophy at this stage of disuse.