Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies
| العنوان: | Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies |
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| المؤلفون: | Daniele Ghezzi, Pio D'Adamo, Clara Benna, Caterina Da Re, Rodolfo Costa, Costanza Lamperti, Mauro Agostino Zordan, Caterina Mariotti, Graziella Uziel, Massimo Zeviani, Cristina Smiderle, Paola Arzuffi, Daria Diodato |
| المساهمون: | D., Ghezzi, P., Arzuffi, M., Zordan, Re, C., C., Lamperti, C., Benna, D'Adamo, ADAMO PIO, D., Diodato, R., Costa, C., Mariotti, G., Uziel, C., Smiderle, M., Zeviani |
| المصدر: | Nature Genetics. 43:259-263 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Electron Transport Complex III: deficiency, Male, BCS1L, genetic [Mitochondrial Proteins], genetic [Electron Transport Complex III], Mitochondrion, Electron Transport Complex III: genetics, medicine.disease_cause, Electron Transport Complex III, pathology [Brain], Drosophila melanogaster: genetics, Membrane Protein, Nervous System Disease, genetic [Membrane Proteins], Genetics, genetic [Nervous System Diseases], Mutation, deficiency [Electron Transport Complex III], Brain, Membrane Proteins: genetics, genetic [Drosophila melanogaster], Mitochondria, Nervous System Diseases: pathology, Drosophila melanogaster, Codon, Nonsense, Gene Knockdown Techniques, Mitochondrial Complex III Deficiency, Mitochondria: metabolism, Female, Human, Adult, Mitochondria: genetics, Biology, Mitochondrial Proteins, pathology [Nervous System Diseases], Mitochondrial Proteins: genetics, Electron transport complex III, medicine, Mitochondrial Protein, Animals, Humans, Progressive encephalopathy, Codon, Mitochondrial protein, Animal, fungi, Membrane Proteins, Nervous System Diseases: genetics, metabolism [Mitochondria], Brain: pathology, genetic [Mitochondria], Nonsense, Gene Knockdown Technique, Immunology, Nervous System Diseases, Neurological impairment |
| الوصف: | Although mutations in CYTB (cytochrome b) or BCS1L have been reported in isolated defects of mitochondrial respiratory chain complex III (cIII), most cIII-defective individuals remain genetically undefined. We identified a homozygous nonsense mutation in the gene encoding tetratricopeptide 19 (TTC19) in individuals from two families affected by progressive encephalopathy associated with profound cIII deficiency and accumulation of cIII-specific assembly intermediates. We later found a second homozygous nonsense mutation in a fourth affected individual. We demonstrated that TTC19 is embedded in the inner mitochondrial membrane as part of two high-molecular-weight complexes, one of which coincides with cIII. We then showed a physical interaction between TTC19 and cIII by coimmunoprecipitation. We also investigated a Drosophila melanogaster knockout model for TTC19 that showed low fertility, adult-onset locomotor impairment and bang sensitivity, associated with cIII deficiency. TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies. |
| وصف الملف: | STAMPA |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25d29c41d0808c577f64b5126e8046f6Test https://doi.org/10.1038/ng.761Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....25d29c41d0808c577f64b5126e8046f6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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