The Role of mTORC1 in Regulating Protein Synthesis and Skeletal Muscle Mass in Response to Various Mechanical Stimuli

Abstract

Skeletal muscle plays a fundamental role in mobility, disease prevention, and quality of life. Skeletal muscle mass is, in part, determined by the rates of protein synthesis, and mechanical loading is a major regulator of protein synthesis and skeletal muscle mass. The mammalian/mechanistic target of rapamycin (mTOR), found in the multi-protein complex, mTORC1, is proposed to play an essential role in the regulation of protein synthesis and skeletal muscle mass. The purpose of this review is to examine the function of mTORC1 in relation to protein synthesis and cell growth, the current evidence from rodent and human studies for the activation of mTORC1 signaling by different types of mechanical stimuli, whether mTORC1 signaling is necessary for changes in protein synthesis and skeletal muscle mass that occur in response to different types of mechanical stimuli, and the proposed molecular signaling mechanisms that may be responsible for the mechanical activation of mTORC1 signaling.

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

“…In general, exercise is anticipated to be related to mTORC1 activity. However, the correlation of mTORC1 activation and the specific type of exercise (such as endurance exercise, which is characterized by the repetition of low to moderate force contractions over a prolonged period of time) is still under investigation (see review of [83]). Since there is no evidence, and one does not see the logic that exercise would lead to carcinogenesis, we consider that proper activation of the mTORC1 pathway is part of healthy living.…”

“…Knowing the correlation of mTORC1 activation and the specific type of exercise (such as endurance exercise, which is characterized by the repetition of low to moderate force contractions over a prolonged period of time) might be a guide to the type of exercise to be recommended to cancer patients, within their physical ability [83]. Non-invasive treatment might then work partly as mTOR inhibitor in a self-regulated manner in the body.…”

Effects of skeletal muscle energy availability on protein turnover responses to exercise

“…Translation initiation is the most well-characterized level of MPS with predominant focus on the mechanistic target of rapamycin (mTOR) protein kinase (Goodman, 2014). mTOR exists in two multi-protein complexes (mTORC1 and mTORC2) with mTORC1 established as the principal regulator of protein translation.…”

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

“…Active Akt has many significant downstream actions; for example, it modulates the phosphorylation of mTOR (mammalian target of rapamycin), a protein kinase that mediates various processes involved in cell proliferation and growth, including protein synthesis (Goodman, 2014). Extensive human and rodent studies have revealed the role of mTOR in the modulation of skeletal muscle mass and protein synthesis in response to different mechanical stimuli (Goodman, 2014). Direct activation of Akt is associated with skeletal muscle hypertrophy, and has also been shown to preserve muscle fibre size in skeletal muscles undergoing atrophy .…”

“…Curiously, a counterintuitive upregulation of mTOR has been reported during muscle inactivity induced by denervation, which might be due to increased amino acid influx from protein degradation pathways, such as the ubiquitin-proteasome system (Quy et al, 2013). Thus, although the precise role of mTOR-related signalling throughout different systems of muscle atrophy remains contentious, mTOR is still considered to be very important in modulating many cellular processes during muscle remodelling (Goodman, 2014).…”