A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome

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• 作者：Z. Assouline^a ; ^b ; M. Jambou^a ; ^b ; M. Rio^a ; ^b ; C. Bole-Feysot^d ; P. de Lonlay^a ; ^b ; ^c ; C. Barnerias^a ; ^b ; I. Desguerre^a ; ^b ; C. Bonnemains^e ; C. Guillermet^f ; J. Steffann^a ; ^b ; A. Munnich^a ; ^b ; ^c ; J.P. Bonnefont^a ; ^b ; ^c ; A. Rö ; tig^a ; ^c ; A.S. Lebre^a ; ^b ; ^c ; ^{anne-sophie.lebre@nck.aphp.fr}
• 关键词：CI ; complex I ; BN-PAGE ; blue native-polyacrylamide gel electrophoresis ; MRI ; Magnetic Resonance Imaging ; mtDNA ; mitochondrial DNA ; RC ; respiratory chain ; kDa ; kilodaltons ; OXPHOS ; oxidative phosphorylation enzymes ; PND ; prenatal diagnosis
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：June, 2012
• 卷：1822
• 期：6
• 页码：1062-1069
• 文件大小：449 K

摘要

Isolated complex I deficiency is a frequent cause of respiratory chain defects in childhood. In this study, we report our systematic approach with blue native PAGE (BN-PAGE) to study mitochondrial respiratory chain assembly in skin fibroblasts from patients with Leigh syndrome and CI deficiency. We describe five new NDUFS4 patients with a similar and constant abnormal BN-PAGE profile and present a meta-analysis of the literature. All NDUFS4 mutations that have been tested with BN-PAGE result in a constant and similar abnormal assembly profile with a complete loss of the fully assembled complex I usually due to a truncated protein and the loss of its canonical cAMP dependent protein kinase phosphorylation consensus site. We also report the association of abnormal brain MRI images with this characteristic BN-PAGE profile as the hallmarks of NDUFS4 mutations and the first founder NDUFS4 mutations in the North-African population.