Mechanosensitive pathways controlling translation regulatory processes in skeletal muscle and implications for adaptation

Abstract

The ability of myofibers to sense and respond appropriately to mechanical signals is one of the primary determinants of the skeletal muscle phenotype. In response to a change in mechanical load, muscle cells alter their protein metabolism, primarily through the regulation of protein synthesis rate. Protein synthesis rates are determined by both translation efficiency and translational capacity within the muscle. Translational capacity is strongly determined by the ribosome content of the muscle; thus the regulation of ribosomal biogenesis by mechanical inputs has been an area of recent interest. Despite the clear association between mechanical signals and changes in protein metabolism, the molecular pathways that link these events are still not fully elucidated. This review focuses on recent studies looking at how mechanosignaling impacts translational events. The role of impaired mechanotransduction in aging is discussed, as is the connection between age-dependent signaling defects and compromised ribosomal biogenesis during mechanical overload. Finally, emerging evidence suggests that the nucleus can act as a mechanosensitive element and that this mode of mechanotransduction may have an important role in skeletal muscle physiology and adaptation.