Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes
Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes
复制标题
DOI：
10.1093/hmg/6.11.1771
复制
发表时间：
1997-10-01
影响因子：
3.5
通讯作者：
Koenig, M
中科院分区：
文献类型：
--
作者：
Campuzano, V;Montermini, L;Koenig, M
弗里德赖希共济失调是一种进行性神经退行性疾病，由共济失调蛋白基因的功能缺失突变引起。为了阐明共济失调蛋白的功能，我们开发了针对该蛋白不同区域的单克隆抗体。这些抗体检测各种人类和小鼠组织和细胞系中的经加工的18 kDa蛋白，其在弗里德赖希共济失调患者中严重减少。通过免疫细胞荧光和免疫细胞电子显微镜，我们发现，共济失调蛋白位于线粒体，与线粒体膜和嵴。对培养细胞中表达的各种截短形式的共济失调蛋白的细胞定位的分析以及在蛋白质成熟期间去除N-末端表位的证据表明，线粒体靶向序列由前20个氨基酸编码。鉴于Friedreich共济失调，维生素E缺乏症和一些神经病之间的共同临床特征，我们的数据表明，共济失调蛋白的减少导致氧化损伤。
Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of Various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.