Related Experiment Video
Updated: Dec 5, 2025
09:47
Author Spotlight: Advancing Mitochondrial Research - mtHyper7 Biosensor for Subcellular Analysis
Published on: June 2, 2023
3.0K
Pathways for Sensing and Responding to Hydrogen Peroxide at the Endoplasmic Reticulum
Jennifer M Roscoe1, Carolyn S Sevier1
1Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
Cells
|October 21, 2020
Summary
The endoplasmic reticulum (ER) generates hydrogen peroxide (H2O2), influencing cell signaling. Protein cysteine oxidation by H2O2 in the ER modulates protein function and limits cellular damage.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- The endoplasmic reticulum (ER) is increasingly recognized as a critical site for cellular redox signaling.
- Hydrogen peroxide (H2O2) is a key reactive oxygen species involved in cell signaling pathways originating from the ER.
Purpose of the Study:
- To review cellular sources of ER-localized H2O2.
- To discuss the impact of H2O2 on ER-localized proteins, specifically BiP, IRE1, and SERCA2.
- To elucidate how cysteine oxidation in these proteins modulates ER functions and cellular signaling.
Main Methods:
- Literature review of studies investigating ER redox signaling.
- Analysis of post-translational modifications of ER proteins by H2O2.
- Examination of signaling pathways influenced by ER-localized H2O2.
Main Results:
- Identified intracellular and extracellular sources of H2O2 within or near the ER.
- Demonstrated that H2O2-mediated cysteine oxidation alters the activity of BiP, IRE1, and SERCA2.
- Showcased how these modifications impact ER signaling events and cellular responses.
Conclusions:
- The ER is a significant source and mediator of H2O2-based signaling.
- Oxidation of specific cysteines in ER proteins like BiP, IRE1, and SERCA2 is a regulatory mechanism.
- Cysteine oxidation by H2O2 can both modulate signaling and protect against cellular damage.
Related Concept Videos
01:24Peroxisomes
18.9K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
18.9K
01:37The Unfolded Protein Response
6.0K
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...
6.0K
01:31Regulation of the Unfolded Protein Response
2.8K
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...
2.8K
01:32Export of Misfolded Proteins out of the ER
4.7K
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...
4.7K
01:27Protein Import into the Peroxisomes
4.8K
Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
4.8K
01:26Protein Modifications in the RER
6.4K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
6.4K