ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2019
Ceramide regulates interaction of Hsd17b4 with Pex5 and function of peroxisomes.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Exercise training is associated with changes in adipocyte size and lipid metabolism in older women: cross-sectional and longitudinal study.BMC geriatrics · 2026Article
- Comprehensive Identification of Lipid-Membrane Protein Interactions via Advanced Proteomics and Extended Lipid-Immobilized Bead Technology.Analytical chemistry · 2025Article
- Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2.Experimental & molecular medicine · 2024Article
- HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity.Breast cancer research and treatment · 2023Article
- Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation.Cell death discovery · 2023Article
- Compartmentalization of Sphingolipid metabolism: Implications for signaling and therapy.Pharmacology & therapeutics · 2022Review
- The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine.Molecules and cells · 2021Article
- Visualization of Ceramide-Associated Proteins in Ceramide-Rich Platforms Using a Cross-Linkable Ceramide Analog and Proximity Ligation Assays With Anti-ceramide Antibody.Frontiers in cell and developmental biology · 2019Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The sphingolipid ceramide regulates beta-oxidation of medium and long chain fatty acids in mitochondria. It is not known whether it also regulates oxidation of very long chain fatty acids (VLCFAs) in peroxisomes. Using affinity chromatography, co-immunoprecipitation, and proximity ligation assays we discovered that ceramide interacts with Hsd17b4, an enzyme critical for peroxisomal VLCFA oxidation and docosahexaenoic acid (DHA) generation. Immunocytochemistry showed that Hsd17b4 is distributed to ceramide-enriched mitochondria-associated membranes (CEMAMs). Molecular docking and in vitro mutagenesis experiments showed that ceramide binds to the sterol carrier protein 2-like domain in Hsd17b4 adjacent to peroxisome targeting signal 1 (PTS1), the C-terminal signal for interaction with peroxisomal biogenesis factor 5 (Pex5), a peroxin mediating transport of Hsd17b4 into peroxisomes. Inhibition of ceramide biosynthesis induced translocation of Hsd17b4 from CEMAMs to peroxisomes, interaction of Hsd17b4 with Pex5, and upregulation of DHA. This data indicates a novel role of ceramide as a molecular switch regulating interaction of Hsd17b4 with Pex5 and peroxisomal function.
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