Mechanistic target of rapamycin complex 1 (mTORC1) and mechanistic target of rapamycin complex 2 (mTORC2) (mTORC1, mTORC2)

Mechanistic target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) are multi-protein kinase complexes that coordinate cellular metabolism, growth, proliferation, and survival by sensing nutrient, energy, growth factor, and stress signals[1][2][3][4][5]. mTORC1, comprising mTOR, Raptor, MLST8, PRAS40, and DEPTOR, is acutely sensitive to inhibition by rapamycin and regulates protein synthesis, lipid biosynthesis, mitochondrial function, and autophagy[1][2][3][4]. mTORC2, containing mTOR, Rictor, and other partners, is less sensitive to rapamycin and involved in cytoskeletal organization, cell survival, and metabolic control[4][5]. Overactivation of these complexes is implicated in cancer, metabolic diseases, neurodegeneration, aging, and cardiovascular disorders, making them important therapeutic targets for multiple drugs, especially rapamycin and its analogs[4][5].

Other names

mammalian target of rapamycin complex 1mammalian target of rapamycin complex 2mTOR complex 1mTOR complex 2rapamycin-sensitive mTOR complex (for mTORC1)rapamycin-insensitive mTOR complex (for mTORC2)FRAP1 complex

Allosteric inhibition of mTORC1 kinase activity (via FKBP12-rapamycin complex binding to mTOR FRB domain)[4][5] Indirect inhibition of translation, lipid synthesis, cell proliferation, and autophagy by blocking mTORC1[1][2][3][4][5] Disruption of mTORC2 formation and signaling with prolonged inhibitor exposure in some cell types[5]