Endoplasmic Reticulum Stress
The endoplasmic reticulum (ER) is an organelle with several essential functions in eukaryotic cells. The ER is both a major intracellular calcium store and the place where proteins are synthesized, folded, modified, and delivered to their final cell surface or extracellular destination. Moreover, in mammalian cells, the ER is the site of sterols and lipids synthesis. Disturbance in any of these functions, which results in the disruption of the proper folding and secretory capacity of the ER and increased load of unfolded proteins in its lumen, defines a condition known as “ER stress.” ER stress activates a complex and multifaceted intracellular signal transduction pathway that is essentially designed to re-establish ER homeostasis. Inability to restore ER functions induces cell death, which is usually in the form of apoptosis. ER stress contributes to the etiology of several human pathologies, including diabetes,...
KeywordsEndoplasmic Reticulum Endoplasmic Reticulum Stress Endoplasmic Reticulum Function Endoplasmic Reticulum Homeostasis Translational Block
Membrane receptors localized in the sarcoplasmic/endoplasmic reticulum that once activated mediates the release of Ca2+ from the ER to the cytosol.
A Ca2+ binding integral protein of the ER that interacts and assists the folding of proteins that carry monoglucosylated N-linked glycans.
A group of heterologous disorders, which include Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob diseases, which arise from the dysfunctional aggregation of proteins in non-native conformations.
Subset of endogenous molecules that have physiological roles within living cells and which acquire immunomodulatory functions when exposed to the extracellular milieu during the cell death process. Once surface exposed or released, DAMPs are sensed by the innate immune system and act as activators of antigen-presenting cells (APCs) to stimulate adaptive immunity.
The molecular apparatus that monitors the maturation and transport of proteins in the ER and targets nonnative conformers for degradation.
The mechanism whereby unfolded or misfolded proteins are re-exported from the ER lumen into the cytosol to undergo proteasomal degradation.
A subunit of eIF2 that recruits Met-tRNAi to the mRNA-40S ribosome complex in its active GTP-binding form. Stress induced eIF2α phosphorylation by a family of protein kinases including PERK, PKR, GCN2, and HRI, prevents the assembly of the eIF2-initiation complex, thereby inhibiting global translation.
Conjugates reduced glutathione to toxic electrophile that have arisen through oxidative stress, for example.
A cell death modality that, in contrast to the physiological caspase mediated-tolerogenic apoptosis, stimulates immunogenicity of the cancer cell along with a protective anticancer immune response in vivo.
Proteins that bind carbohydrates.
A family of cellular proteins that mediate the correct assembly and disassembly of nascent polypeptides, by the reversible interaction with nascent polypeptide chains.
The most energetically favorable state adopted by a protein, which usually corresponds to the conformation with the lowest free energy.
Transcription factor that can induce the expression of anti-oxidant proteins.
A 26S multiprotein complex that catalyses the degradation of polyubiquitylated proteins.
An enzyme belonging to the thiol-disulphide oxidoreductases family of proteins that catalyzes the oxidation, isomerization, and reduction of disulphide bonds.
A group of chemically reactive molecules and free radical molecules deriving from the incomplete reduction of molecular oxygen. Examples of which are superoxide and peroxide.
Activated IRE1 is able to utilize its endoribonuclease domain in the degradation of mRNA which harbor a specific XBP-1-like consensus site.
A complex network of eukaryotic cell organelles that is central to and mediates the folding, maturation, and trafficking of secreted and transmembrane proteins.
A pump situated in the membrane of the sarcoplasmic/endoplasmic reticulum that couples ATP hydrolysis to the import of Ca2+ from the cytosol to the ER lumen.
A transmembrane protein that exposes its carboxyl terminus into the cytosol.
A transmembrane protein that exposes its amino terminus into the cytosol.
- Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, Yuan CL, Krokowski D, Wang S, Hatzoglou M, Kilberg MS, Sartor MA, Kaufman RJ (2013) ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol 15:481–490CrossRefPubMedPubMedCentralGoogle Scholar