mTORC1 vs mTORC2 – what's the difference?

mTOR (the protein) forms two separate complexes that do different jobs. mTORC1 regulates protein synthesis, autophagy, and growth in response to nutrients and growth factors – and it's the one rapamycin blocks. mTORC2 phosphorylates Akt/PKB and affects cell survival and glucose metabolism – and critically, it is not directly blocked by rapamycin (in mTORC2, the partner proteins Rictor and mSin1 cover the FRB site where the FKBP12-rapamycin pair docks). Long-term rapamycin dosing eventually suppresses mTORC2 too, indirectly – the likely source of the insulin-resistance side effect seen with daily dosing.

Side by side

Evidence	What it means	Studies
H	Human study	14
A	Animal model	45
M	Molecular — cells, biochemistry, structure	89
R	Review — secondary literature, not a new result	26
PP	Preprint, not peer-reviewed	3

mTORC1 – 177 studies total. "mTOR Complex 1; regulates protein synthesis, autophagy, and growth in response to nutrients and growth factors."

Evidence	What it means	Studies
H	Human study	1
A	Animal model	5
M	Molecular — cells, biochemistry, structure	19
R	Review — secondary literature, not a new result	11

mTORC2 – 36 studies total. "mTOR Complex 2; phosphorylates Akt/PKB, affects cell survival and glucose metabolism." mTORC2 THO2009 M – rapamycin does NOT fully block mTORC1 either – using Torin1 (which jams the active site directly), this study showed rapamycin leaves important mTORC1 jobs running, notably 4E-BP1 phosphorylation.

Why the distinction matters

mTORC1 is rapamycin's direct target, so its studies are where you'll find the growth/autophagy/protein-synthesis effects; mTORC2 is where the metabolic side effects trace back to, and it only shows up because chronic rapamycin dosing eventually reaches it indirectly – a consequence of chronic exposure, not of the effect the drug is used for. This is the basis of one of the Atlas's flagged open questions: whether a dosing strategy that hits mTORC1 (for the benefit) while sparing mTORC2 (avoiding the metabolic cost) is achievable, and if so, whether it's a matter of drug selectivity, dose, or timing. See the full open question.

Related entities

Open in the Atlas explorer