دورية أكاديمية
QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease
| العنوان: | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
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| المؤلفون: | Virginia Guarani, Claude Jardel, Dominique Chrétien, Anne Lombès, Paule Bénit, Clémence Labasse, Emmanuelle Lacène, Agnès Bourillon, Apolline Imbard, Jean-François Benoist, Imen Dorboz, Mylène Gilleron, Eric S Goetzman, Pauline Gaignard, Abdelhamid Slama, Monique Elmaleh-Bergès, Norma B Romero, Pierre Rustin, Hélène Ogier de Baulny, Joao A Paulo, J Wade Harper, Manuel Schiff |
| المصدر: | eLife, Vol 5 (2016) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | QIL1, MICOS, mitochondrial disease, early-onset fatal mitochondrial encephalopathy, 3-methylglutaconic aciduria, liver disease, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain function in patient muscle. QIL1 absence in patients’ fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/17163Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.17163 |
| الوصول الحر: | https://doaj.org/article/c2eb5d8eb5b14293a741ed6e1db3525aTest |
| رقم الانضمام: | edsdoj.2eb5d8eb5b14293a741ed6e1db3525a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.17163 |