Lysosome
The organelle on whose surface mTORC1 is activated. Nutrient signals converge here: mTORC1 must be physically recruited to the lysosomal membrane before Rheb can switch it on.
The place where the decision is made.
Amino-acid sensing, Rheb access, TFEB regulation and autophagosome fusion all happen on or in this one organelle.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 4 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2016 | M | Lysosomal recruitment of TSC2 is a universal response to cellular stress DEM2016 Lysosomal recruitment of TSC2 is a universal response to cellular stress that inhibits mTORC1. |
| 2012 | M | Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 BAR2012 Ragulator is the guanine-nucleotide exchange factor activating the Rag GTPases on the lysosome. |
| 2011 | M | mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 Showed amino acid sensing starts INSIDE the lysosome: amino acids accumulate in the lumen and the v-ATPase relays that signal outward ('inside-out') to Ragulator-Rag. A surprising twist on where the cell measures its nutrient status. |
| 2010 | M | Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids SAN2010 Established WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb lives. Amino acids work by controlling this translocation. |