ArticleBiochimica et biophysica acta2015
Ceramide channels: destabilization by Bcl-xL and role in apoptosis.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- Ceramides as Biomarkers and Pharmacological Targets in Heart Failure Pathophysiology.Biomolecules · 2026Review
- Acid Ceramidase Inhibition Disrupts Ceramide Homeostasis and Induces Mitochondrial Apoptosis in IDH1-Mutant Oligodendroglioma.Research square · 2026Article
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- A novel prenylflavonoid with efficacy in cancer therapy by targeting ceramide-orchestrated signaling.Frontiers in pharmacology · 2026Article
- Lipidomic and transcriptomic analysis and its therapeutic implications in Chinese Kazakh patients with esophageal squamous cell carcinoma.BMC cancer · 2025Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- RBM10 deficiency promotes brain metastasis by modulating sphingolipid metabolism in a BBB model of EGFR mutant lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Targeted lipidomics meets transcriptomics: how cinobufagin rewires fatty acid, sphingolipid, and glycerophospholipid metabolism to combat hepatoma cell growth.Frontiers in pharmacology · 2025Article
- The effects of restraint stress on ceramide metabolism disorders in the rat liver: the role of CerS6 in hepatocyte injury.Lipids in health and disease · 2024Article
- Profiling lipidomic changes in dengue-resistant and dengue-susceptible strains of Colombian Aedes aegypti after dengue virus challenge.PLoS neglected tropical diseases · 2023Article
- KLF15 suppresses tumor growth and metastasis in Triple-Negative Breast Cancer by downregulating CCL2 and CCL7.Scientific reports · 2022Article
- Sorting-free metabolic profiling uncovers the vulnerability of fatty acid β-oxidation in in vitro quiescence models.Molecular systems biology · 2022Article
- Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.Blood · 2022Article
- HumanInternational journal of biological sciences · 2022Article
- Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment.Oncology reports · 2021Article
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- Neutral Ceramidase Is Required for the Reproduction of Brown Planthopper,Frontiers in physiology · 2021Article
- Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Ceramide is a bioactive sphingolipid involved in mitochondrial-mediated apoptosis. Our data suggest that ceramides directly regulate a key initiation step in apoptosis: mitochondrial outer membrane permeabilization (MOMP). MOMP allows release of intermembrane space proteins to the cytosol, inducing the execution of the cell. Ceramides form channels in planar phospholipid membranes and outer membranes of isolated mitochondria, channels large enough to facilitate passage of proteins released during MOMP. Bcl-xL inhibits MOMP in vivo and inhibits the formation of ceramide channels in vitro. However the significance of Bcl-xL's regulation of ceramide channel formation within cells was untested. We engineered Bcl-xL point mutations that specifically affect the interaction between ceramide and Bcl-xL to probe the mechanism of ceramide channel regulation and the role of ceramide channels in apoptosis. Using these mutants and fluorescently-labeled ceramide, we identified the hydrophobic groove on Bcl-xL as the critical ceramide binding site and regulator of ceramide channel formation. Bcl-xL mutants with weakened interaction with ceramide also have reduced ability to interfere with ceramide channel formation. Some mutants have similar altered ability to inhibit both ceramide and Bax channel formation, whereas others act differentially, suggesting distinct but overlapping binding sites. To probe the relative importance of these channels in apoptosis, Bcl-xL mutant proteins were stably expressed in Bcl-xL deficient cells. Weakening the inhibition of either Bax or ceramide channels decreased the ability of Bcl-xL to protect cells from apoptosis in a stimulus-dependent manner. These studies provide the first in vivo evidence for the role of ceramide channels in MOMP.
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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.