Expression of yeast NDI1 rescues a Drosophila complex I assembly defect.
Expression of yeast NDI1 rescues a Drosophila complex I assembly defect.
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DOI：
10.1371/journal.pone.0050644
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Walker DW
中科院分区：
文献类型：
--
作者：
Cho J;Hur JH;Graniel J;Benzer S;Walker DW
线粒体电子传递链（ETC）功能的缺陷与许多神经退行性疾病、癌症和衰老有关。线粒体复合物I（NADH脱氢酶）是ETC中最大和最复杂的酶，具有45个亚基，来自两个独立的基因组。复合物I的生物发生是一个复杂的过程，需要多个步骤、酶和组装因子。在这里，我们报告的生成和表征的果蝇模型的复杂I组装因子缺陷。我们表明，CG 7598（dCIA 30），果蝇同源的人类复合物I装配因子Ndufaf 1，是必要的适当的复合物I组装。dCIA 30的表达减少导致复合物I全酶带在蓝色-天然聚丙烯酰胺凝胶电泳中的损失和在分离的线粒体中的NADH：泛醌氧化还原酶活性的损失。由dCIA 30的突变或RNAi引起的复合物I组装缺陷在果蝇的发育和成年期都有影响，包括蛹期的发育停滞和成年期的应激抗性降低。单亚基酵母替代性NADH脱氢酶Ndi 1的表达可以部分或全部挽救与复合物I组装缺陷相关的表型。我们的工作表明，CG 7598/dCIA 30是Ndufaf 1的功能同源物，并增加了越来越多的证据表明，转基因NDI 1表达是一个可行的治疗所产生的疾病复杂I缺陷。
Defects in mitochondrial electron transport chain (ETC) function have been implicated in a number of neurodegenerative disorders, cancer, and aging. Mitochondrial complex I (NADH dehydrogenase) is the largest and most complicated enzyme of the ETC with 45 subunits originating from two separate genomes. The biogenesis of complex I is an intricate process that requires multiple steps, subassemblies, and assembly factors. Here, we report the generation and characterization of a Drosophila model of complex I assembly factor deficiency. We show that CG7598 (dCIA30), the Drosophila homolog of human complex I assembly factor Ndufaf1, is necessary for proper complex I assembly. Reduced expression of dCIA30 results in the loss of the complex I holoenzyme band in blue-native polyacrylamide gel electrophoresis and loss of NADH:ubiquinone oxidoreductase activity in isolated mitochondria. The complex I assembly defect, caused by mutation or RNAi of dCIA30, has repercussions both during development and adulthood in Drosophila, including developmental arrest at the pupal stage and reduced stress resistance during adulthood. Expression of the single-subunit yeast alternative NADH dehydrogenase, Ndi1, can partially or wholly rescue phenotypes associated with the complex I assembly defect. Our work shows that CG7598/dCIA30 is a functional homolog of Ndufaf1 and adds to the accumulating evidence that transgenic NDI1 expression is a viable therapy for disorders arising from complex I deficiency.
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DOI：
10.4061/2011/438370
发表时间：
2010-12-06
期刊：
Parkinson's disease
影响因子：
--
作者：
Barber-Singh J;Seo BB;Matsuno-Yagi A;Yagi T
通讯作者：
Yagi T
影响因子：
11.4
作者：
Dunning, C. J. R.;McKenzie, M.;Ryan, M. T.
通讯作者：
Ryan, M. T.
DOI：
10.1111/j.1432-1033.1991.tb15775.x
发表时间：
1991-02-14
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
MARRES, CAM;DEVRIES, S;GRIVELL, LA
通讯作者：
GRIVELL, LA
影响因子：
4.8
作者：
Seo, Byoung Boo;Nakamaru-Ogiso, Eiko;Yagi, Takao
通讯作者：
Yagi, Takao
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.