دورية أكاديمية
OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect
| العنوان: | OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect |
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| المؤلفون: | Kyle Thompson, Nicole Mai, Monika Oláhová, Filippo Scialó, Luke E Formosa, David A Stroud, Madeleine Garrett, Nichola Z Lax, Fiona M Robertson, Cristina Jou, Andres Nascimento, Carlos Ortez, Cecilia Jimenez‐Mallebrera, Steven A Hardy, Langping He, Garry K Brown, Paula Marttinen, Robert McFarland, Alberto Sanz, Brendan J Battersby, Penelope E Bonnen, Michael T Ryan, Zofia MA Chrzanowska‐Lightowlers, Robert N Lightowlers, Robert W Taylor |
| المصدر: | EMBO Molecular Medicine, Vol 10, Iss 11, Pp n/a-n/a (2018) |
| بيانات النشر: | Springer Nature, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | encephalopathy, insertase, mitochondria, OXA1L, OXPHOS, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative phosphorylation complexes IV and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported to impair assembly of complexes I and V only. We report a patient presenting with severe encephalopathy, hypotonia and developmental delay who died at 5 years showing complex IV deficiency in skeletal muscle. Whole exome sequencing identified biallelic OXA1L variants (c.500_507dup, p.(Ser170Glnfs*18) and c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially, expression of wild‐type human OXA1L in patient fibroblasts rescued the complex IV and V defects. Targeted depletion of OXA1L in human cells or Drosophila melanogaster caused defects in the assembly of complexes I, IV and V, consistent with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA‐encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of these OXA1L variants and demonstrate that OXA1L is required for the assembly of multiple respiratory chain complexes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| العلاقة: | https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test |
| DOI: | 10.15252/emmm.201809060 |
| الوصول الحر: | https://doaj.org/article/0d713560574b49dfa1120e2d8edbb05cTest |
| رقم الانضمام: | edsdoj.0d713560574b49dfa1120e2d8edbb05c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.201809060 |