2011 January ; 12(1): 21–35. doi:10.1038/nrm3025. | Roberto Zoncu#, David M. Sabatini, and Alejo Efeyan#
The Target of Rapamycin (TOR) signaling pathway plays a crucial role in integrating energy and nutrient availability with cell growth and division. In mammals, two distinct complexes of mTOR, mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2), regulate various cellular processes. mTORC1, composed of mTOR and raptor, is activated by amino acids and growth factors, while mTORC2, composed of mTOR and rictor, is regulated by growth factors. mTORC1 controls protein synthesis, ribosome biogenesis, and autophagy, whereas mTORC2 regulates cytoskeletal organization and the phosphorylation of AGC kinases such as Akt, SGK, and PKC. Dysregulation of mTOR signaling is implicated in diabetes, cancer, and ageing. In diabetes, chronic overactivation of mTORC1 leads to impaired insulin sensitivity and increased lipogenesis. In cancer, mTORC1 and mTORC2 promote tumor growth and survival through various mechanisms. In ageing, mTORC1 inhibition can extend lifespan by enhancing autophagy and reducing cellular damage. The identification of novel regulators and substrates of mTOR has advanced our understanding of its regulatory network, and the development of mTOR inhibitors offers potential therapeutic strategies for diseases associated with mTOR dysfunction.The Target of Rapamycin (TOR) signaling pathway plays a crucial role in integrating energy and nutrient availability with cell growth and division. In mammals, two distinct complexes of mTOR, mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2), regulate various cellular processes. mTORC1, composed of mTOR and raptor, is activated by amino acids and growth factors, while mTORC2, composed of mTOR and rictor, is regulated by growth factors. mTORC1 controls protein synthesis, ribosome biogenesis, and autophagy, whereas mTORC2 regulates cytoskeletal organization and the phosphorylation of AGC kinases such as Akt, SGK, and PKC. Dysregulation of mTOR signaling is implicated in diabetes, cancer, and ageing. In diabetes, chronic overactivation of mTORC1 leads to impaired insulin sensitivity and increased lipogenesis. In cancer, mTORC1 and mTORC2 promote tumor growth and survival through various mechanisms. In ageing, mTORC1 inhibition can extend lifespan by enhancing autophagy and reducing cellular damage. The identification of novel regulators and substrates of mTOR has advanced our understanding of its regulatory network, and the development of mTOR inhibitors offers potential therapeutic strategies for diseases associated with mTOR dysfunction.