Homoplasmic deleterious MT-ATP6/8 mutations in adult patients
| Autor: | Claude Jardel, Norma B. Romero, Sandrine Filaut, Isabelle Serre, Benoit Rucheton, Francis Haraux, Maria del Mar Amador, Anne Lombès, Sarah Leonard-Louis, T. Maisonobe |
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| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Protéines et Systèmes Membranaires (LPSM), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Mitochondrial DNA Mitochondrial Diseases Mitochondrial disease [SDV]Life Sciences [q-bio] oxidative phosphorylation Oxidative phosphorylation Biology Hybrid Cells Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine medicine Humans Glycolysis Muscle Skeletal Molecular Biology Gene Cells Cultured Homoplasmy ATP synthase homoplasmy cybrids High-Throughput Nucleotide Sequencing Cell Biology Sequence Analysis DNA Fibroblasts Mitochondrial Proton-Translocating ATPases medicine.disease Molecular biology mitochondrial disease 030104 developmental biology MT-ATP6 Mutation biology.protein Molecular Medicine Female 030217 neurology & neurosurgery |
| Zdroj: | Mitochondrion Mitochondrion, 2020, ⟨10.1016/j.mito.2020.08.004⟩ |
| Popis: | To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects. |
| Databáze: | OpenAIRE |
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