ArticleThe Journal of biological chemistry2013
Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 202 citations in OpenAlex.
- An extra virgin olive oil-enriched chocolate spread positively modulates insulin-resistance markers compared with a palm oil-enriched one in healthy young adults: A double-blind, cross-over, randomised controlled trial.Diabetes/metabolism research and reviews · 2022Trial
- Novel Insight in Idiopathic Normal Pressure Hydrocephalus (iNPH) Biomarker Discovery in CSF.International journal of molecular sciences · 2021Trial
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Ceramides: A Biologically Attractive Lipid and Advances in Acquisition Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression.EMBO reports · 2026Article
- Bioenergetic failure in diabetic peripheral neuropathy: from glucotoxicity to multidimensional metabolic imbalance.Journal of neurology · 2026Review
- Hesperidin alleviates systemic inflammation and oxidative stress by remodeling adipose tissue lipid metabolism in periparturient dairy cows.Journal of animal science and biotechnology · 2026Article
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.EBioMedicine · 2026Article
- Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025Review
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- Obesity promotes ARDS by modulating ceramide transfer protein-ceramide pathway and exacerbating oxidative stress/apoptosis in alveolar macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Protein kinase C epsilon activation improves early survival in an acute porcine model of controlled hemorrhage.Scientific reports · 2025Article
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Molecular insights into the unique properties of the blood-circulating proteasome.Journal of extracellular biology · 2025Article
- Article
- Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease.Scientific reports · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Ceramide is a key intermediate in the pathway of sphingolipid biosynthesis and is an important intracellular messenger. We recently generated a ceramide synthase 2 (CerS2) null mouse that cannot synthesize very long acyl chain (C22-C24) ceramides. This mouse displays severe and progressive hepatopathy. Significant changes were observed in the sphingolipid profile of CerS2 null mouse liver, including elevated C16-ceramide and sphinganine levels in liver and in isolated mitochondrial fractions. Because ceramide may be involved in reactive oxygen species (ROS) formation, we examined whether ROS generation was affected in CerS2 null mice. Levels of a number of anti-oxidant enzymes were elevated, as were lipid peroxidation, protein nitrosylation, and ROS. ROS were generated from mitochondria due to impaired complex IV activity. C16-ceramide, sphingosine, and sphinganine directly inhibited complex IV activity in isolated mitochondria and in mitoplasts, whereas other ceramide species, sphingomyelin, and diacylglycerol were without effect. A fluorescent analog of sphinganine accumulated in mitochondria. Heart mitochondria did not display a substantial alteration in the sphingolipid profile or in complex IV activity. We suggest that C16-ceramide and/or sphinganine induce ROS formation through the modulation of mitochondrial complex IV activity, resulting in chronic oxidative stress. These results are of relevance for understanding modulation of ROS signaling by sphingolipids.
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