Promotion of plasmalogen biosynthesis reverse lipid changes in a Barth Syndrome cell model |
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| Institution: | 1. Centre de Recherche du CHU de Québec, Axe Neurosciences, 2705, Boulevard Laurier, Québec (Québec), G1V 4G2, Canada;2. Faculté de Pharmacie, Pavillon Ferdinand-Vandry, 1050, avenue de la Médecine, Université Laval, Québec (Québec), G1V 0A6, Canada;3. Med-Life Discoveries LP, 407-15 Innovation Boulevard, Saskatoon, SK S7N 2X8, Canada;2. Department of Pathology, CHRU Bretonneau, F-37044 Tours CEDEX 9, France;4. Faculté de Pharmacie, Université de Tours, F-37200 Tours, France;1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4K1, Canada;2. Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada;1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;2. University of the Chinese Academy of Sciences, Beijing 100049, China;3. Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland;1. Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, 2705 Laurier Boulevard, Quebec City, Qc G1V 4G2, Canada;2. Faculty of Pharmacy, Laval University, 1050, Avenue de la Médecine, Quebec City, Qc G1V 0A6, Canada;3. Med-Life Discoveries LP, 104-407 Downey Road, Saskatoon, SK S7N 4L8, Canada |
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| Abstract: | In Barth syndrome (BTHS) mutations in tafazzin leads to changes in both the quantities and the molecular species of cardiolipin (CL), which are the hallmarks of BTHS. Contrary to the well-established alterations in CL associated with BTHS; recently a marked decrease in the plasmalogen levels in Barth specimens has been identified. To restore the plasmalogen levels, the present study reports the effect of promotion of plasmalogen biosynthesis on the lipidome of lymphoblasts derived from Barth patients as well as on cell viability, mitochondria biogenesis, and mitochondrial membrane potential. High resolution 31P NMR phospholipidomic analysis showed an increase in the levels of plasmenylethanolamine (the major plasmalogen in lymphoblasts), which reached values comparable to the control and a compensatory decrease in the levels of its diacyl-PE counterpart. Importantly, 31P NMR showed a significant increase in the levels of CL, while not altering the levels of monolysocardiolipin. Mass spectrometry measurements showed that the promotion of plasmalogen biosynthesis did not change the molecular species profile of targeted phospholipids. In addition, promotion of plasmalogen biosynthesis did not impact on cellular viability, although it significantly decrease mitochondria copy number and restored mitochondrial membrane potential. Overall, the results showed the efficacy of the promotion of plasmalogen biosynthesis on increasing the CL levels in a BTHS cell model and highlight the potential beneficial effect of a diet supplemented with plasmalogen precursors to BTHS patients. |
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