Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways
| Autor: | Catherine Florentz, Marie Sissler, Gert C. Scheper, Agnès Gaudry, Marjo S. van der Knaap, Laura van Berge, Josta T. Kevenaar, Emiel Polder |
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| Přispěvatelé: | Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Child Neurology Department, Fondazione IRCCS Istituto Neurologico, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Other departments, Pediatric surgery, NCA - Brain mechanisms in health and disease |
| Rok vydání: | 2013 |
| Předmět: |
Mitochondrial Diseases
MESH: Mitochondria [SDV]Life Sciences [q-bio] Aspartate-tRNA Ligase Cell Mutation Missense Biology Transfection MESH: Leukoencephalopathies Compound heterozygosity Biochemistry MESH: Spinal Cord Pathogenesis Leukoencephalopathy White matter 03 medical and health sciences 0302 clinical medicine Leukoencephalopathies medicine Humans Missense mutation MESH: Aspartate-tRNA Ligase Molecular Biology 030304 developmental biology Genetics chemistry.chemical_classification MESH: Mutation Missense 0303 health sciences MESH: Humans MESH: Transfection MESH: Immunohistochemistry MESH: Mitochondrial Diseases Cell Biology medicine.disease Immunohistochemistry Molecular biology Enzyme assay Mitochondria 3. Good health HEK293 Cells medicine.anatomical_structure Enzyme Spinal Cord chemistry MESH: HEK293 Cells MESH: Brain Stem biology.protein 030217 neurology & neurosurgery Brain Stem |
| Zdroj: | Biochemical Journal, 450, 345-350. Portland Press Ltd. Biochemical Journal Biochemical Journal, Portland Press, 2013, 450 (2), pp.345-350. ⟨10.1042/BJ20121564⟩ van Berge, L, Kevenaar, J, Polder, E, Gaudry, A, Florentz, C, Sissler, M, van der Knaap, M S & Scheper, G C 2013, ' Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways ', Biochemical Journal, vol. 450, pp. 345-350 . https://doi.org/10.1042/BJ20121564 Biochemical journal, 450(2), 345-350. Portland Press Ltd. |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20121564 |
| Popis: | International audience; The autosomal recessive white matter disorder LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is caused by mutations in DARS2, coding for mtAspRS (mitochondrial aspartyl-tRNA synthetase). Generally, patients are compound heterozygous for mutations in DARS2. Many different mutations have been identified in patients, including several missense mutations. In the present study, we have examined the effects of missense mutations found in LBSL patients on the expression, enzyme activity, localization and dimerization of mtAspRS, which is important for understanding the cellular defect underlying the pathogenesis of the disease. Nine different missense mutations were analysed and were shown to have various effects on mtAspRS properties. Several mutations have a direct effect on the catalytic activity of the enzyme; others have an effect on protein expression or dimerization. Most mutations have a clear impact on at least one of the properties of mtAspRS studied, probably resulting in a small contribution of the missense variants to the mitochondrial aspartylation activity in the cell. |
| Databáze: | OpenAIRE |
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