mTORC1 regulation by GCN2/ATF4 under transient starvation

Ascertain whether mechanistic target of rapamycin complex 1 (mTORC1) is regulated by the general amino acid sensors GCN2 and ATF4 in transiently starved cells, in contrast to prolonged amino acid deprivation where GCN2 and ATF4 drive Sestrin-mediated transcriptional responses.

Background

In prolonged amino acid deprivation, GCN2 detects uncharged tRNAs, leading to eIF2α phosphorylation and ATF4 induction that transcriptionally upregulates Sestrins, which feed back into mTORC1 control.

The review notes that the applicability of GCN2/ATF4-mediated regulation to transient starvation (acute, short-term nutrient limitation) is unknown, motivating targeted investigation of mTORC1’s regulation in this regime.