Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling

Trends Cell Biol. 2012 May;22(5):274-82. doi: 10.1016/j.tcb.2012.02.006. Epub 2012 Mar 21.


Many cellular processes including apoptosis, autophagy, translation, energy metabolism, and inflammation are controlled by the mammalian target of rapamycin (mTOR) kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR). Although both of these signaling nodes have attracted wide attention in fundamental cell biology and drug discovery, crosstalk between the two pathways has emerged only very recently. mTOR complex 1 (mTORC1) operates both upstream and downstream of ER stress signals, which can either enhance or antagonize the anabolic output of mTORC1. Upon prolonged ER stress, mTORC1 contributes to apoptotic signaling by suppressing the survival kinase Akt through feedback inhibition. Likewise, chronic ER stress obstructs activation of Akt by mTOR complex 2. This review surveys our knowledge of mTOR-ER stress intersections and highlights potential therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress*
  • Humans
  • Protein Unfolding
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism


  • TOR Serine-Threonine Kinases