Mtor

mTOR is the acronym for "mechanistic target of Rapamycin", a regulatory protein found in all mammals that indirectly binds the immunosuppressive agent Rapamycin. The mTOR gene is located on chromosome 1p36.22 and codes for the mTOR protein.

The mTOR protein is an enzyme important for cell survival, growth, proliferation and motility, which adds a phosphate group to several other proteins and enzymes, thus activating them. Thus, mTOR is part of signal transduction in the body and the beginning of a cascade of signalling pathways. The misregulation of the mTOR signalling pathway favours the development of metabolic diseases such as diabetes, obesity and tumours. Increased mTORC1 activity has been demonstrated in the skin of acne patients(Melnik B 2018).

In the cell, the regulator protein is found in 2 functionally and structurally different protein complexes, which are called mTORC1 and mTORC2.

Activation of mTORC1 leads to phosphorylation of two key proteins that regulate protein translation: 4E-BP1 (eukaryotic initiation factor 4E (eIF-4E) binding protein-1) and S6K1 (protein S6 kinase 1).

Inhibition of mTOR is responsible for the immunodeficient effects of Rapamycin. T cells, cells of blood and lymph vessels, smooth muscle cells and tumour cells are particularly sensitive to inhibition of mTOR. In hereditary cystic kidney disease, mTOR is upregulated in the epithelial cells of renal cysts. In the animal model, rapamycin leads to the apoptosis of the cyst wall cells and thus inhibits the growth of the cysts. mTORC1 overactivation leads to the degradation of the amino acid glutamine, resulting in an increase in the level of the stress hormone FGF21. With the administration of glutamine, the FGF21 levels could be lowered, thus preventing the physiological impairments.

The misregulation of the mTOR signalling pathway favours the development of metabolic diseases such as diabetes, obesity and tumours. Numerous tumors are characterized by a misregulated mTORC1 signaling network and glutamine dependence.

Currently, inhibitors of mTORC1 such as rapamycin are used as immunosuppressive agents. The latest findings suggest that the treatment of glutamine-dependent tumours with rapamycin can slow down tumour growth and counteract a derailment of the metabolism.

1. Melnik B et al (2018) Acne and rosacea. In: G Plewig G et al (ed.) Braun-Falco`s Dermatology, Venerology and Allergology. Springer Reference Medicine S 1306