ArticleJournal of lipid research2022
Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich's ataxia.
Article in Journal of lipid research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Impaired Glur2 palmitoylation in cerebellar Purkinje cells of a Friedreich ataxia mouse model.Experimental neurology · 2026Article
- Neuropathology of Friedreich ataxia and its links to metabolic pathways.Neurodegenerative disease management · 2026Review
- Advances in Gene and Cellular Therapy in Friedreich Ataxia.Molecular diagnosis & therapy · 2026Review
- Impact of Omaveloxolone on Serum Lipids in Patients with Friedreich Ataxia: A 1-Year Real-World Analysis.CNS drugs · 2026Observational
- Article
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- Role of SCAP in regulation of pancreatic homeostasis, pancreatitis, and tumorigenesis.Oncogene · 2026Article
- Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- Dodecanedioic Acid: Alternative Carbon Substrate or Toxic Metabolite?Biomolecules · 2025Article
- Review
- Insulin Sensitivity and Insulin Secretion in Adults With Friedreich's Ataxia: The Role of Skeletal Muscle.The Journal of clinical endocrinology and metabolism · 2025Observational
- Metabolic pathways of eicosanoids-derivatives of arachidonic acid and their significance in skin.Cellular & molecular biology letters · 2025Review
- Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia.Nanomaterials (Basel, Switzerland) · 2024Article
- Article
- Interplay of FXN expression and lipolysis in white adipocytes plays a critical role in insulin sensitivity in Friedreich's ataxia mouse model.Scientific reports · 2024Article
- Frataxin Loss Promotes Angiotensin II-Induced Endothelial-to-Mesenchymal Transition.Journal of the American Heart Association · 2024Article
- Hypermetabolic state is associated with circadian rhythm disruption in mouse and human cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma.Cancer research · 2024Article
- Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.JCI insight · 2024Article
- METTL17 is an Fe-S cluster checkpoint for mitochondrial translation.Molecular cell · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a triplet guanine-adenine-adenine (GAA) repeat expansion in intron 1 of the FXN gene, which leads to decreased levels of the frataxin protein. Frataxin is involved in the formation of iron-sulfur (Fe-S) cluster prosthetic groups for various metabolic enzymes. To provide a better understanding of the metabolic status of patients with FRDA, here we used patient-derived fibroblast cells as a surrogate tissue for metabolic and lipidomic profiling by liquid chromatography-high resolution mass spectrometry. We found elevated HMG-CoA and β-hydroxybutyrate-CoA levels, implying dysregulated fatty acid oxidation, which was further demonstrated by elevated acyl-carnitine levels. Lipidomic profiling identified dysregulated levels of several lipid classes in FRDA fibroblast cells when compared with non-FRDA fibroblast cells. For example, levels of several ceramides were significantly increased in FRDA fibroblast cells; these results positively correlated with the GAA repeat length and negatively correlated with the frataxin protein levels. Furthermore, stable isotope tracing experiments indicated increased ceramide synthesis, especially for long-chain fatty acid-ceramides, in FRDA fibroblast cells compared with ceramide synthesis in healthy control fibroblast cells. In addition, PUFA-containing triglycerides and phosphatidylglycerols were enriched in FRDA fibroblast cells and negatively correlated with frataxin levels, suggesting lipid remodeling as a result of FXN deficiency. Altogether, we demonstrate patient-derived fibroblast cells exhibited dysregulated metabolic capabilities, and their lipid dysfunction predicted the severity of FRDA, making them a useful surrogate to study the metabolic status in FRDA.
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