ArticleThe Journal of biological chemistry2011
Novel pathway of ceramide production in mitochondria: thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.JCI insight · 2018Trial
- Association of Clinical Severity in Autism Spectrum Disorder with Biomolecules Involved in Lipid Metabolism, Inflammation and miRNAs.Biomolecules · 2026Article
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- Glycosphingolipids: from metabolism to chemoenzymatic total synthesis.Organic & biomolecular chemistry · 2024Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Article
- Engineered Lipidic Nanomaterials Inspired by Sphingomyelin Metabolism for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Defining the lipidome of Arabidopsis leaf mitochondria: Specific lipid complement and biosynthesis capacity.Plant physiology · 2023Article
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- The Role of Ceramide in Inherited Retinal Disease Pathology.Advances in experimental medicine and biology · 2023Article
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life.Progress in retinal and eye research · 2022Review
- Ceramides and Acute Kidney Injury.Seminars in nephrology · 2022Review
- Measurement of neutral ceramidase activity in vitro and in vivo.Analytical biochemistry · 2022Review
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Compartmentalization of Sphingolipid metabolism: Implications for signaling and therapy.Pharmacology & therapeutics · 2022Review
- Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats.International journal of molecular sciences · 2022Article
- The aetiology and molecular landscape of insulin resistance.Nature reviews. Molecular cell biology · 2021Review
- Hyperlipidemic Conditions Impact Force-Induced Inflammatory Response of Human Periodontal Ligament Fibroblasts Concomitantly Challenged withInternational journal of molecular sciences · 2021Article
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Reports suggest that excessive ceramide accumulation in mitochondria is required to initiate the intrinsic apoptotic pathway and subsequent cell death, but how ceramide accumulates is unclear. Here we report that liver mitochondria exhibit ceramide formation from sphingosine and palmitoyl-CoA and from sphingosine and palmitate. Importantly, this activity was markedly decreased in liver from neutral ceramidase (NCDase)-deficient mice. Moreover, the levels of ceramide were dissimilar in liver mitochondria of WT and NCDase KO mice. These results suggest that NCDase is a key participant of ceramide formation in liver mitochondria. We also report that highly purified liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activities. Increased accessibility of palmitoyl-CoA to the mitochondrial matrix with the pore-forming peptide zervamicin IIB resulted in 2-fold increases in palmitoyl-CoA hydrolysis by thioesterase. This increased hydrolysis was accompanied by an increase in ceramide formation, demonstrating that both outer membrane and matrix localized thioesterases can regulate ceramide formation. Also, ceramide formation might occur both in the outer mitochondrial membrane and in the mitochondrial matrix, suggesting the existence of distinct ceramide pools. Taken together, these results suggest that the reverse activity of NCDase contributes to sphingolipid homeostasis in this organelle in vivo.
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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.