ArticleCellular and molecular life sciences : CMLS2021
Murine deficiency of peroxisomal L-bifunctional protein (EHHADH) causes medium-chain 3-hydroxydicarboxylic aciduria and perturbs hepatic cholesterol homeostasis.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Broad-Coverage Lipidomics Reveals Temporal Lipid Remodeling and Candidate Serum Biomarkers After Acute Spinal Cord Injury in Rats.Biomedicines · 2026Article
- Odd-Chain Dicarboxylic Acid Feeding Produces a Glutaric Aciduria Type 1-Like Metabolic Signature in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Horizontal and longitudinal targeted metabolomics in healthy pregnancy and gestational diabetes mellitus.Acta diabetologica · 2025Article
- A Multiomic Network Approach to Uncover Disease Modifying Mechanisms of Inborn Errors of Metabolism.Journal of inherited metabolic disease · 2025Article
- Lipidomics reveals effect of EHHADH in lung squamous cell.Cell biology and toxicology · 2025Article
- Robust hierarchical co-clustering for exploring toxicogenomic biomarkers and their chemical regulators.Scientific reports · 2025Article
- Identification of biomarkers for endometriosis based on summary-data-based Mendelian randomization and machine learning.Medicine · 2025Article
- LncRNA Gm35585 transcriptionally activates the peroxidase EHHADH against diet-induced fatty liver.Experimental & molecular medicine · 2025Article
- Modelling Peroxisomal Disorders in Zebrafish.Cells · 2025Review
- CLCN5 inhibits tumorigenesis and fatty acid accumulation in clear cell renal cell carcinoma by regulating Enoyl CoA hydratase and 3-Hydroxyacyl CoA dehydrogenase.International journal of medical sciences · 2025Article
- Peroxisome Metabolism Pathway and EHHADH Expression are Downregulated in Macrophages in Neutrophilic Asthma.Allergy, asthma & immunology research · 2025Article
- Identifying the key role of mitochondrial respiration and lipid metabolism in regulating axillary osmidrosis through proteomics analysis.Archives of dermatological research · 2024Article
- Sirtuin-5 Is Recruited to Hepatic Peroxisomes in Mice Fed Dodecanedioic Acid but Has Little Impact on the Peroxisomal Succinylome.Biomolecules · 2024Article
- Nicotinamide mitigates visceral leishmaniasis by regulating inflammatory response and enhancing lipid metabolism.Parasites & vectors · 2024Article
- Comparative transcriptome and methylome of polar bears, giant and red pandas reveal diet-driven adaptive evolution.Evolutionary applications · 2024Article
- Article
- The biochemistry and physiology of long-chain dicarboxylic acid metabolism.The Biochemical journal · 2023Review
- Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Ameliorative Effect of EthanolicInternational journal of molecular sciences · 2022Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Peroxisomes play an essential role in the β-oxidation of dicarboxylic acids (DCAs), which are metabolites formed upon ω-oxidation of fatty acids. Genetic evidence linking transporters and enzymes to specific DCA β-oxidation steps is generally lacking. Moreover, the physiological functions of DCA metabolism remain largely unknown. In this study, we aimed to characterize the DCA β-oxidation pathway in human cells, and to evaluate the biological role of DCA metabolism using mice deficient in the peroxisomal L-bifunctional protein (Ehhadh KO mice). In vitro experiments using HEK-293 KO cell lines demonstrate that ABCD3 and ACOX1 are essential in DCA β-oxidation, whereas both the bifunctional proteins (EHHADH and HSD17B4) and the thiolases (ACAA1 and SCPx) have overlapping functions and their contribution may depend on expression level. We also show that medium-chain 3-hydroxydicarboxylic aciduria is a prominent feature of EHHADH deficiency in mice most notably upon inhibition of mitochondrial fatty acid oxidation. Using stable isotope tracing methodology, we confirmed that products of peroxisomal DCA β-oxidation can be transported to mitochondria for further metabolism. Finally, we show that, in liver, Ehhadh KO mice have increased mRNA and protein expression of cholesterol biosynthesis enzymes with decreased (in females) or similar (in males) rate of cholesterol synthesis. We conclude that EHHADH plays an essential role in the metabolism of medium-chain DCAs and postulate that peroxisomal DCA β-oxidation is a regulator of hepatic cholesterol biosynthesis.
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