Andrei V. Budanov
Showed that Sestrin stress sensors physically hold mTORC1 back through the GATOR complex
postdoc, Michael Karin lab, UC San Diego · Assistant Professor, VCU Massey Cancer Center · now Ussher Assistant Professor, Biochemistry, Trinity College Dublin
Budanov Lab, Trinity College Dublin ↗
Portrait: Trinity College Dublin
In flies (LEE2010), showed loss of Sestrin lets TOR run unchecked, producing fat accumulation, mitochondrial dysfunction, muscle wasting, heart failure — reversible by inhibiting TOR or activating AMPK; established a TOR–Sestrin negative feedback loop. Follow-up (PAR2014): Sestrins bind GATOR2 directly, blocking mTORC1 recruitment to the lysosome — an AMPK-independent brake.
Traces back to his postdoc with Michael Karin (Sestrin1/2 as p53 targets activating AMPK to inhibit mTOR after DNA damage, 2008 Cell). Now at Trinity College Dublin.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2010 | A | Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies LEE2010 Loss of Sestrin in flies lets TOR run unchecked, causing fat/mitochondrial/muscle/heart pathology reversible by blocking TOR or activating AMPK. |
| 2014 | M | Sestrins inhibit mTORC1 kinase activation through the GATOR complex PAR2014 Sestrins block mTORC1 by binding GATOR2, preventing mTOR from reaching the lysosome. |