Related Experiment Video
Updated: Dec 17, 2025
10:12
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
2.5K
Endoplasmic Reticulum (ER) Stress Response Failure in Diseases
Kashi Raj Bhattarai1, Manoj Chaudhary1, Hyung-Ryong Kim2
1Department of Pharmacology and Institute of New Drug Development, Jeonbuk National University Medical School, 54896, Jeonju, Republic of Korea.
Trends in Cell Biology
|June 21, 2020
Summary
Endoplasmic reticulum (ER) stress response failure is linked to metabolic diseases. This study identifies conditions contributing to ER stress failure in metabolic and age-related diseases like obesity and diabetes.
Area of Science:
- Cellular Biology
- Metabolic Disease Research
- Pathogenesis Studies
Background:
- Emerging evidence links endoplasmic reticulum (ER) stress response or sensing failure to metabolic dysfunction.
- ER stress is a cellular state of imbalance within the ER lumen.
- Dysregulation of ER homeostasis is implicated in various diseases.
Purpose of the Study:
- To identify and compile conditions associated with ER stress response failure.
- To investigate the role of ER stress failure in metabolic pathogenesis.
- To explore the connection between ER stress failure and age-related diseases, including obesity and diabetes.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of studies reporting ER stress markers in metabolic and age-related conditions.
- Categorization of identified conditions based on pathogenesis.
Main Results:
- Compilation of diverse conditions characterized by ER stress response failure.
- Evidence supporting the involvement of ER stress failure in obesity and type 2 diabetes.
- Identification of potential links between ER stress failure and other age-related pathologies.
Conclusions:
- Endoplasmic reticulum (ER) stress response failure is a significant factor in metabolic and age-related diseases.
- Understanding these failure conditions is crucial for developing targeted therapeutic strategies.
- Further research is warranted to elucidate the precise mechanisms and therapeutic potential.
Related Concept Videos
01:17Role of ER in the Secretory Pathway
6.7K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
6.7K
01:37The Unfolded Protein Response
6.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.1K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
01:32Export of Misfolded Proteins out of the ER
4.8K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.8K
01:27Post-translational Translocation of Proteins to the RER
7.2K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
7.2K
01:29Protein Folding Quality Check in the RER
4.9K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.9K