FIGURE 10.

Summary of myostatin signaling and how mechanical overload affects signaling outcomes. This schematic (constructed with BioRender.com, with permission) provides a summary of myostatin (MSTN) signaling in skeletal muscle and how mechanical overload in rodents or humans affects signaling outcomes based on the research cited in-text. Upon ligand binding, MSTN leads to the phosphorylation of SMAD2/3, which causes the formation of the SMAD2/3/4 complex. This complex can then enter nuclei and affect the expression of genes that negatively impact muscle size and growth (i.e., genomic effects). A putative nongenomic effect of MSTN signaling includes the inhibition of AKT phosphorylation, and this can lead to diminished protein synthesis rates. Notably, blue arrows and inhibitor indicators illustrate how resistance exercise affects aspects of MSTN signaling. As discussed in main text, acute and/or chronic resistance training has been documented to upregulate myostatin inhibitors (follistatin and FSTL3), reduce SMAD2/3/4 nuclear translocation through JNK1/2 activation, and reduce MSTN mRNA levels through decreasing transcription rates.