Endoplasmic Reticulum and the Unfolded Protein Response

Abstract

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies.

Androgen-regulated metabolism and biosynthesis in prostate cancer

“…ER stress is often associated with increased ribosome biogenesis and elevated rates of splicing and transcript turnover. As rate-limiting organelles in protein and transcript processing the ER and the nucleolus, are significant sensors and responders to the metabolic stress (Bravo et al 2013, Grummt 2013. The ER plays a role as a principal site for protein folding and the nucleolus in the processing and assembly of ribonucleoprotein complexes to sustain protein synthesis and splicing.…”

Inhibition of IRE1 modifies hypoxic regulation of G6PD, GPI, TKT, TALDO1, PGLS and RPIA genes expression in U87 glioma cells

“…The signa ling enzyme IRE1 has two distinct catalytic domains: serine/thre onine kinase and endoribonuclease. Both domains contributed to ERN1 signaling [30]. The IRE1as sociated protein kinase autophosphorylates and di merizes this enzyme in the endoplasmic reticulum membrane, leading to the activation of its endoribo nuclease domain, and has some additional functions [7].…”

“…The IRE1as sociated protein kinase autophosphorylates and di merizes this enzyme in the endoplasmic reticulum membrane, leading to the activation of its endoribo nuclease domain, and has some additional functions [7]. Endoribonuclease activity is responsible for deg radation of a specific subset of mRNA and initiation of the preXBP1 (Xbox binding protein 1) mRNA splicing that stimulates the expression of more than five hundreds of unfolded protein response-specific genes [6,30,31]. It is possible that this activation of the ERN1 endoribonuclease is a result of its interac tion with other sensorsignalling systems of endo plasmic reticulum stress.…”

Effect of chromium disilicide and titanium nitride nanoparticles on the expression of NAMPT, E2F8, FAS, TBX3, IL13RA2, and UPS7 genes in mouse liver

“…Multiple studies have clarified the link between endoplasmic reticulum stress, which controls numerous processes including cell proliferation and surviving and various diseases including cancer and metabolic diseases [30][31][32][33]. It is possible that long-term treatment of mice to chromium disilicide and titanium dioxide nanoparticles also led to endoplasmic reticulum stress and altered expression of stress related genes, which are integrated into the unfolded protein response signaling pathways and regulate cell proliferation and apoptosis.…”