ArticleThe EMBO journal2001
The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers.
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Who cites it
226 citing papers in PubMed, 591 citations in OpenAlex.
- Mitochondria-endoplasmic reticulum-lipid droplet crosstalk in lipid metabolic reprogramming in type 2 diabetes mellitus.Journal of lipid research · 2026Review
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Intracellular Membrane Contact Sites in Skeletal Muscle Cells.Membranes · 2025Review
- TMCO1 is upregulated in breast cancer and regulates the response to pro-apoptotic agents in breast cancer cells.Cell death discovery · 2024Article
- Thermodynamic Considerations on the Biophysical Interaction between Low-Energy Electromagnetic Fields and Biosystems.Membranes · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma.International journal of genomics · 2024Article
- The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.Biomolecules · 2023Review
- The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis inInternational journal of molecular sciences · 2023Article
- A Dominant-Negative Mutant of ANXA7 Impairs Calcium Signaling and Enhances the Proliferation of Prostate Cancer Cells by Downregulating the IP3 Receptor and the PI3K/mTOR Pathway.International journal of molecular sciences · 2023Article
- Adenosine monophosphate deaminase in the endoplasmic reticulum-mitochondria interface promotes mitochondrial CaJournal of diabetes investigation · 2023Article
- Editorial: The evolving picture of CaFrontiers in physiology · 2023Article
- IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines.EXCLI journal · 2023Article
- Neither too much nor too little: mitochondrial calcium concentration as a balance between physiological and pathological conditions.Frontiers in molecular biosciences · 2023Review
- Structural basis of CaBMB reports · 2022Review
- Endoplasmic-reticulum-stress-induced lipotoxicity in human kidney epithelial cells.Toxicology research · 2022Article
- Article
166 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism of action of the anti-apoptotic oncogene Bcl-2 is still largely obscure. We have recently shown that the overexpression of Bcl-2 in HeLa cells reduces the Ca2+ concentration in the endoplasmic reticulum ([Ca2+]er) by increasing the passive Ca2+ leak from the organelle. To investigate whether this Ca2+ depletion is part of the mechanism of action of Bcl-2, we mimicked the Bcl-2 effect on [Ca2+]er by different pharmacological and molecular approaches. All conditions that lowered [Ca2+]er protected HeLa cells from ceramide, a Bcl-2-sensitive apoptotic stimulus, while treatments that increased [Ca2+]er had the opposite effect. Surprisingly, ceramide itself caused the release of Ca2+ from the endoplasmic reticulum and thus [Ca2+] increased both in the cytosol and in the mitochondrial matrix, paralleled by marked alterations in mitochondria morphology. The reduction of [Ca2+]er levels, as well as the buffering of cytoplasmic [Ca2+] changes, prevented mitochondrial damage and protected cells from apoptosis. It is therefore concluded that the Bcl-2-dependent reduction of [Ca2+]er is an important component of the anti-apoptotic program controlled by this oncogene.
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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.