ArticleCell death discovery2024
The endoplasmic reticulum pool of Bcl-xL prevents cell death through IP3R-dependent calcium release.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
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Who cites it
13 citing papers in PubMed.
- Intermembrane coupling between Bcl-xL and the IPCell reports · 2026Article
- The evolving global landscape of first-in-class oncology drug innovation.Signal transduction and targeted therapy · 2026Review
- UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids.Cell death & disease · 2026Article
- Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Targeting Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs): A Novel Therapeutic Strategy for Diabetic Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Mitochondrial Calcium Channels and MAM Interaction in Calcium Homeostasis Dysregulation in Parkinson's Disease.Neurochemical research · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- USP18 attenuates endoplasmic reticulum stress via the PERK-eIF2α-ATF4 axis to reduce apoptosis in hepatocellular carcinoma cells.Scientific reports · 2025Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- ONC201 (Dordaviprone) Induces Integrated Stress Response and Death in Cervical Cancer Cells.Biomolecules · 2025Article
- Phosphorylation of Bok at Ser-8 blocks its ability to suppress IPCell communication and signaling : CCS · 2025Article
- Mitochondrial Bcl-xL promotes brain synaptogenesis by controlling non-lethal caspase activation.iScience · 2023Article
- BCL-XL Overexpression Protects Pancreatic β-Cells against Cytokine- and Palmitate-Induced Apoptosis.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Apoptosis plays a role in cell homeostasis in both normal development and disease. Bcl-xL, a member of the Bcl-2 family of proteins, regulates the intrinsic mitochondrial pathway of apoptosis. It is overexpressed in several cancers. Bcl-xL has a dual subcellular localisation and is found at the mitochondria as well as the endoplasmic reticulum (ER). However, the biological significance of its ER localisation is unclear. In order to decipher the functional contributions of the mitochondrial and reticular pools of Bcl-xL, we generated genetically modified mice expressing exclusively Bcl-xL at the ER, referred to as ER-xL, or the mitochondria, referred to as Mt-xL. By performing cell death assays, we demonstrated that ER-xL MEFs show increased vulnerability to apoptotic stimuli but are more resistant to ER stress. Furthermore, ER-xL MEFs displayed reduced 1,4,5-inositol trisphosphate receptor (IP3R)-mediated ER calcium release downstream of Phospholipase C activation. Collectively, our data indicate that upon ER stress, Bcl-xL negatively regulates IP3R-mediated calcium flux from the ER, which prevents ER calcium depletion and maintains the UPR and subsequent cell death in check. This work reveals a moonlighting function of Bcl-xL at the level of the ER, in addition to its well-known role in regulating apoptosis through the mitochondria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.