Academic Journal
Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.
| العنوان: | Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. |
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| المؤلفون: | Wortmann, S.B., Vaz, F.M., Gardeitchik, T., Vissers, L.E.L.M., Renkema, G.H., Schuurs-Hoeijmakers, J.H.M., Kulik, W., Lammens, M.M.Y., Christin, C., Kluijtmans, L.A.J., Rodenburg, R.J.T., Nijtmans, L.G.J., Grunewald, A., Klein, C., Gerhold, J.M., Kozicz, L.T., Hasselt, P.M. van, Harakalova, M., Kloosterman, W., Baric, I., Pronicka, E., Ucar, S.K., Naess, K., Singhal, K.K., Krumina, Z., Gilissen, C.F.H.A., Bokhoven, J.H.L.M. van, Veltman, J.A., Smeitink, J.A.M., Lefeber, D.J., Spelbrink, J.N., Wevers, R.A., Morava, E., Brouwer, A.P.M. de |
| المصدر: | Nature Genetics, 44, 7, pp. 797-802 |
| سنة النشر: | 2012 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | DCN MP - Plasticity and memory IGMD 9: Renal disorder, DCN NN - Brain networks and neuronal communication, DCN PAC - Perception action and control IGMD 4: Glycostation disorders, IGMD 4: Glycostation disorders, IGMD 8: Mitochondrial medicine, IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism, IGMD 8: Mitochondrial medicine NCMLS 5: Membrane transport and intracellular motility, NCMLS 6: Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory, NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders |
| الوصف: | Contains fulltext : 108785.pdf (Publisher’s version ) (Closed access) ; Using exome sequencing, we identify SERAC1 mutations as the cause of MEGDEL syndrome, a recessive disorder of dystonia and deafness with Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. We localized SERAC1 at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. A phospholipid analysis in patient fibroblasts showed elevated concentrations of phosphatidylglycerol-34:1 (where the species nomenclature denotes the number of carbon atoms in the two acyl chains:number of double bonds in the two acyl groups) and decreased concentrations of phosphatidylglycerol-36:1 species, resulting in an altered cardiolipin subspecies composition. We also detected low concentrations of bis(monoacyl-glycerol)-phosphate, leading to the accumulation of free cholesterol, as shown by abnormal filipin staining. Complementation of patient fibroblasts with wild-type human SERAC1 by lentiviral infection led to a decrease and partial normalization of the mean ratio of phosphatidylglycerol-34:1 to phosphatidylglycerol-36:1. Our data identify SERAC1 as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. ; 01 juli 2012 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | http://hdl.handle.net/2066/108785 |
| DOI: | 10.1038/ng.2325 |
| الاتاحة: | http://hdl.handle.net/2066/108785 https://doi.org/10.1038/ng.2325 |
| رقم الانضمام: | edsbas.561F3181 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ng.2325 |
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