Fig. 2

Dysfunction of the TSC complex causes mTORC1 hyperactivation through Rheb, which leads to metabolic and molecular changes. The TSC complex deactivates the RAS homolog enriched in brain (Rheb) by causing GTP to be cleaved from it. After stimulation by growth factor, the TSC complex is phosphorylated and its GTPase-activating protein activity is decreased. Similarly, dysfunction of the TSC complex is caused by loss-of-function mutations of TSC1/TSC2 in the tuberous sclerosis complex (TSC). All of these factors activate Rheb to stimulate mammalian target of rapamycin (mTOR) complex 1 (mTORC1). mTORC1 directly regulates lipid, nucleotide, and protein synthesis to promote cell cycle progression and also inhibits autophagy. It ultimately causes excessive division and proliferation of cells to form hamartomas in multiple organs. AKT RACα serine/threonine-protein kinase; ERK extracellular-signal-regulated kinase; GLUT1 solute carrier family 2, facilitated glucose transporter member 1 (also known as glucose transporter type 1, erythrocyte/brain); mLST8 target of rapamycin complex subunit LST8; mTORC2 mammalian target of rapamycin complex 2; Raptor regulatory-associated protein of mTOR; RICTO rapamycin-insensitive companion of mTOR; ROS reactive oxygen species; SLC1A5 neutral amino acid transporter B(0); TBC1D7 TBC1 domain family member 7