Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration - International Review of Cell and Molecular Biology - page 242

Figure 5.4 The ER modulates important metabolic pathways during ER stres s . PERK
induces global attenuation in protein anabolism, and also favors lipid synthesis, both
effects via eIF2 α phosphorylation. IRE1 cooperates with these responses and stimulates
mitochondrial biogenesis through the regulation of master metabolic switches, such as
PGC1 α , mTOR, AMPK and FOXO1. ATF6, on the other hand, stimulates lipid utilization.
Calcium released by IP3R increases mitochondrial activity during ER stress, in order to
revert energy imbalance.
5.1. UPR-Mediated Regulation of Master Metabolic Switches
The best-known effect of UPR on cellular metabolism is the attenuation of
general protein translation via eIF2α phosphorylation. Such negative regu-
lation not only reduces protein load in the ER but also increases ATP avail-
ability for processes such as protein folding and degradation.
As already mentioned, conditions of low nutrient supply are known
to induce the UPR as well as autophagy. The relationship between these
two responses becomes clear considering that nutrient deprivation increases