Fig. 1

Signals, pathways, targets, and outputs of the mTOR signalling. mTOR is a protein kinase that complexes with several proteins composing the mTOR complex 1 (mTORC1) and mTORC2. Both are activated by growth factors and mTORC1 also depends on amino acids for its translocation into the lysosome membrane where it becomes fully activated. These processes involve the activation of the Rag GTPases Rag A or Rag B and Rag C or D complexed with Ragulator complex in addition to the Ras homolog enriched in brain (RHEB). Additional signals that result in mTORC1 activation include insulin and inflammation, that act through the insulin-like growth factor-1 (IGF-1)/AKT and the TNF/Tuberous Sclerosis Complex (TSC) axis, respectively. On the other hand, inactivation of mTORC1 occurs under stress conditions, such as energy starvation, a process dependent on AMPK; hypoxia, through upregulation of REDD1, endoplasmatic reticulum stress (UPR) by upregulation of Sestrin 2 (SESN2); and DNA damage, by activation of the p53 transcriptional program. mTORC2 becomes activated in the plasma and mitochondrial membranes, a subpopulation of endosomal vesicles and in the nucleus, through site-specific processes. Each complex has a plethora of substrates, such as but not exclusively 4E-binding proteins (4E-BP), S6 kinases (S6K), unc-51-like kinase (ULK1) and Transcription factor EB (TFEB) for mTORC1 and glucocorticoid-induced kinases (SGK), protein kinase C (PKC) and AKT for mTORC2. The main biological processes regulated by mTORC1 include protein, lipid and nucleotides synthesis, metabolism and autophagy; and cytoskeleton reorganization, glucose homeostasis and metabolism for mTORC2, whose activation results in cell survival, growth, proliferation and migration