| Reference : Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function an... |
| Scientific journals : Article | |||
| Scientific journals : Article | |||
| http://hdl.handle.net/10993/24251 | |||
| Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. | |
| English | |
| Wortmann, Saskia B. [> >] | |
| Vaz, Frederic M. [> >] | |
| Gardeitchik, Thatjana [> >] | |
| Vissers, Lisenka E. L. M. [> >] | |
| Renkema, G. Herma [> >] | |
| Schuurs-Hoeijmakers, Janneke H. M. [> >] | |
| Kulik, Wim [> >] | |
| Lammens, Martin [> >] | |
| Christin, Christin [> >] | |
| Kluijtmans, Leo A. J. [> >] | |
| Rodenburg, Richard J. [> >] | |
| Nijtmans, Leo G. J. [> >] | |
| Grünewald, Anne [> >] | |
| Klein, Christine [> >] | |
| Gerhold, Joachim M. [> >] | |
| Kozicz, Tamas [> >] | |
| van Hasselt, Peter M. [> >] | |
| Harakalova, Magdalena [> >] | |
| Kloosterman, Wigard [> >] | |
| Baric, Ivo [> >] | |
| Pronicka, Ewa [> >] | |
| Ucar, Sema Kalkan [> >] | |
| Naess, Karin [> >] | |
| Singhal, Kapil K. [> >] | |
| Krumina, Zita [> >] | |
| Gilissen, Christian [> >] | |
| van Bokhoven, Hans [> >] | |
| Veltman, Joris A. [> >] | |
| Smeitink, Jan A. M. [> >] | |
| Lefeber, Dirk J. [> >] | |
| Spelbrink, Johannes N. [> >] | |
| Wevers, Ron A. [> >] | |
| Morava, Eva [> >] | |
| de Brouwer, Arjan P. M. [> >] | |
| 2012 | |
| Nature genetics | |
| 44 | |
| 7 | |
| 797-802 | |
| Yes (verified by ORBilu) | |
| International | |
| 1061-4036 | |
| 1546-1718 | |
| United States | |
| [en] Amino Acid Sequence ; Carboxylic Ester Hydrolases/genetics/metabolism ; Cardiolipins/genetics/metabolism ; Cell Line, Transformed ; Cell Line, Tumor ; Cholesterol/genetics/metabolism ; Deafness/genetics/metabolism ; Dystonia/genetics/metabolism ; Exome ; Fibroblasts/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Mitochondria/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Oxidative Phosphorylation ; Phosphatidylglycerols/genetics/metabolism ; Phospholipids/genetics/metabolism ; Sequence Alignment | |
| [en] 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. | |
| Researchers ; Students | |
| http://hdl.handle.net/10993/24251 |
There is no file associated with this reference.
All documents in ORBilu are protected by a user license.
