Related Experiment Video
Updated: Jun 24, 2026
10:50
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Intricate links between ER stress and apoptosis
1Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Molecular Cell
|March 31, 2009
Summary
Bax inhibitor-1 (BI-1) neutralizes apoptosis by interacting with Bax. New research reveals BI-1 also inhibits IRE1alpha, a key player in the unfolded protein response (UPR), linking ER stress and apoptosis.
Area of Science:
- Molecular biology
- Cellular stress response
- Apoptosis research
Background:
- Bax inhibitor-1 (BI-1) is known to counteract apoptosis by binding to Bax.
- The unfolded protein response (UPR) is a critical cellular pathway activated by endoplasmic reticulum (ER) stress.
Purpose of the Study:
- To investigate the direct molecular interactions of Bax inhibitor-1 (BI-1).
- To elucidate the role of BI-1 in the context of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).
Main Methods:
- The study involved biochemical assays to examine protein interactions.
- Functional assays were used to assess the impact of BI-1 on UPR mediators.
Main Results:
- Lisbona et al. demonstrate that BI-1 directly inhibits IRE1alpha, a central mediator of the UPR.
- This inhibition by BI-1 establishes a functional link between apoptosis regulation and ER stress signaling.
Conclusions:
- Bax inhibitor-1 (BI-1) plays a dual role in cellular homeostasis, regulating both apoptosis and ER stress.
- The findings reveal a novel mechanism of crosstalk between the apoptotic pathway and the UPR, mediated by BI-1's inhibition of IRE1alpha.
Related Concept Videos
01:17Role of ER in the Secretory Pathway
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...
01:31Regulation of the Unfolded Protein Response
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...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...