mTORC1 / mTORC2 (mTOR complexes)

The mechanistic target of rapamycin (mTOR) kinase assembles into two structurally and functionally distinct multi-protein complexes: mTORC1, defined by its scaffold subunit Raptor, and mTORC2, defined by Rictor. mTORC1 integrates signals from amino acids, insulin, energy status and growth factors to promote anabolic processes — principally ribosome biogenesis via S6K1 and 4E-BP1 phosphorylation — and to suppress autophagy by phosphorylating ULK1; it is acutely sensitive to allosteric inhibition by rapamycin. mTORC2, by contrast, is rapamycin-insensitive under standard conditions, phosphorylates AKT at Ser473 to regulate cell survival and cytoskeletal organisation, and feeds into the PI3K/AKT/FOXO axis. In the context of ageing, chronic mTORC1 hyperactivity is considered a principal driver of anabolic imbalance and suppressed autophagy, while the differential contributions of each complex to lifespan extension — particularly when mTOR is inhibited globally — remain an active area of investigation.