How does mTOR increase muscle protein synthesis?

mTOR is a key molecule that regulates protein synthesis in muscle fibers and other cells.

It acts as a sensor of both the internal and external environments of a cell and “decides” whether conditions are right to switch on production of proteins.

By integrating various cell signals, mTOR monitors several conditions such as: availability of amino acids, mechanical load, glucose levels, overall energy status, inflammation, growth factors, and circulating levels of hormones. When these conditions are correct (e.g. there is an abundance of available amino acids), mTOR activates various biochemical pathways that lead to protein production.

For example, mTOR stimulates cell structures (or ‘organelles’) called ribosomes. Ribosomes work by linking individual amino acids together to build large protein chains. mTOR also promotes the growth of new ribosomes, allowing cells to produce more proteins.

mTORC1

mTOR doesn’t work in isolation. Rather, it joins up with other molecules to form “multi-protein complexes.” The other molecules in these complexes help to regulate the activity of mTOR and also respond to various cell signals.

There are two distinct complexes of which mTOR is a key component:

Of both of these, mTORC1 is the most widely studied and understood. When mTOR is activated, the larger mTORC1 complex acts on various signalling pathways to boost protein production.

mTORC1 also stimulates the production of fats and cholesterol, as well as new mitochondrial components (see the Mitochondrial Biogenesis blog for more detail).

KEY POINTS

As explained earlier, mTOR (or the mTORC1 complex) acts as a sensor of the internal and external environments of a cell. It can switch on production of proteins and cell growth in response to various stimuli.

Exposing your muscles to a mechanical load (e.g. lifting weights) triggers several different biochemical signalling cascades in your muscle cells that lead to muscle protein synthesis. In one of these pathways, studies show that mechanical stretch of skeletal muscle leads to the generation of a molecule called phosphatidic acid (PA). PA then activates the mTORC1 complex, leading to increased protein synthesis.

Amino acids are the building blocks of proteins. When a cell has a good supply of amino acids, it can increase its production of proteins.

The mTORC1 complex is sensitive to levels of amino acids inside cells, particularly the essential amino acid leucine. When levels rise, mTORC1 switches on protein production.

If you’re looking to build muscle, it is therefore important to consume enough protein, particularly post-exercise. This will provide your muscle cells with a good supply of amino acids for muscle protein synthesis.

Growth factors are special signalling proteins that stimulate the growth of cells. Some growth factors, such as insulin, can also be classified as hormones – chemical messages transported in the bloodstream.

Both insulin and a closely related molecule, called Insulin-like growth factor 1 (IGF-1), can activate mTORC1 and promote protein synthesis. This mechanism allows cells to produce protein and grow following meals, when insulin levels increase in response to rising blood sugar levels.

When insulin and IGF-1 bind to their respective receptors, they trigger a signalling cascade known as the PI3K/AKT/mTOR pathway. This pathway ultimately activates mTORC1 and switches on protein production.

Another hormone, testosterone, may also interact with this pathway to promote protein synthesis. For this reason, it’s important to maintain healthy testosterone levels to optimize muscle protein synthesis and ensure your muscles develop.

KEY POINTS