کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1999614 1065865 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients
چکیده انگلیسی

Dysfunction of complex I (NADH:ubiquinone oxidoreductase; CI), the largest enzyme of the oxidative phosphorylation (OXPHOS) system, often results in severe neuromuscular disorders and early childhood death. Mutations in its seven mitochondrial and 38 nuclear DNA-encoded structural components can only partly explain these deficiencies. Recently, CI assembly chaperones NDUFAF1 and B17.2L were linked to CI deficiency, but it is still unclear by which mechanism. To better understand their requirement during assembly we have studied their presence in CI subcomplexes in a cohort of CI deficient patients using one- and two-dimensional blue-native PAGE. This analysis revealed distinct differences between their associations to subcomplexes in different patients. B17.2L occurred in a 830 kDa subcomplex specifically in patients with mutations in subunits NDUFV1 and NDUFS4. Contrasting with this seemingly specific requirement, the previously described NDUFAF1 association to 500–850 kDa intermediates did not appear to be related to the nature and severity of the CI assembly defect. Surprisingly, even in the absence of assembly intermediates in a patient harboring a mutation in translation elongation factor G1 (EFG1), NDUFAF1 remained associated to the 500–850 kDa subcomplexes. These findings illustrate the difference in mechanism between B17.2L and NDUFAF1 and suggest that the involvement of NDUFAF1 in the assembly process could be indirect rather than direct via the binding to assembly intermediates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 91, Issue 2, June 2007, Pages 176–182
نویسندگان
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