ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. 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, 31 citations in OpenAlex.
- Charcot-Marie-Tooth disease variants of HSPB1 progressively alter neuromuscular signalling.Disease models & mechanisms · 2026Article
- Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?Molecular neurodegeneration · 2026Review
- Review
- A Case Report and Literature Review of Charcot-Marie-Tooth Disease Type 2F in a Family.Degenerative neurological and neuromuscular disease · 2025Article
- Current Treatment Methods for Charcot-Marie-Tooth Diseases.Biomolecules · 2024Review
- A novel HSPB1Prostaglandins & other lipid mediators · 2023Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- Unraveling the Mechanisms of Ch-SeNP Cytotoxicity against Cancer Cells: Insights from Targeted and Untargeted Metabolomics.Nanomaterials (Basel, Switzerland) · 2023Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Insights Into the Role of Heat Shock Protein 27 in the Development of Neurodegeneration.Frontiers in molecular neuroscience · 2022Review
- A Compound Heterozygous Pathogenic Variant inJournal of clinical neurology (Seoul, Korea) · 2021Article
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- The ins and outs of serine and glycine metabolism in cancer.Nature metabolism · 2021Review
- Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results.International journal of molecular sciences · 2020Review
- Myeloperoxidase and Septic Conditions Disrupt Sphingolipid Homeostasis in Murine Brain Capillaries In Vivo and Immortalized Human Brain Endothelial Cells In Vitro.International journal of molecular sciences · 2020Article
- Plasma lipidomic biomarker analysis reveals distinct lipid changes in vascular dementia.Computational and structural biotechnology journal · 2020Article
- Exploiting Sphingo- and Glycerophospholipid Impairment to Select Effective Drugs and Biomarkers for CMT1A.Frontiers in neurology · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- S1P/S1P Receptor Signaling in Neuromuscolar Disorders.International journal of molecular sciences · 2019Review
- The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer's Disease and Other Neurodegenerative Disorders.Molecular neurobiology · 2019Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide. Given that Hsp27 is a chaperone protein, we examined its role in regulating ceramide synthases (CerSs), an enzyme family responsible for catalyzing generation of the sphingolipid ceramide. We determined that CerSs colocalized with Hsp27, and upon the presence of S135F mutants, CerS1 lost its colocalization with mitochondria suggesting that decreased mitochondrial ceramides result from reduced mitochondrial CerS localization rather than decreased CerS activity. Mitochondria in mutant cells appeared larger with increased interconnectivity. Furthermore, mutant cell lines demonstrated decreased mitochondrial respiratory function and increased autophagic flux. Mitochondrial structural and functional changes were recapitulated by blocking ceramide generation pharmacologically. These results suggest that mutant Hsp27 decreases mitochondrial ceramide levels, producing structural and functional changes in mitochondria leading to neuronal degeneration.-Schwartz, N. U., Linzer, R. W., Truman, J.-P., Gurevich, M., Hannun, Y. A., Senkal, C. E., Obeid, L. M. Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.
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