JournalClub: mTORC1 activity repression by late endosomal phosphatidylinositol 3,4-bisphosphate

The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth in response to nutrients. Marat et al. found that the lipid phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], which, when generated at the cell surface, is linked to stimulation of mTORC1 and promotion of cell growth, does the opposite when synthesized at the late endosome or lysosome. In cells deprived of nutrients, PI(3,4)P2 was produced at lysosomes, where it recruited an inhibitor of mTORC1. The results elucidate the complex regulation of mTORC1, which is altered in human diseases such as cancer and neurodegeneration.