TY - JOUR
T1 - Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes
AU - Campuzano, Victoria
AU - Montermini, Laura
AU - Lutz, Yves
AU - Cova, Lidia
AU - Hindelang, Colette
AU - Jiralerspong, Sarn
AU - Trottier, Yvon
AU - Kish, Stephen J.
AU - Faucheux, Baptiste
AU - Trouillas, Paul
AU - Authier, François J.
AU - Dürr, Alexandra
AU - Mandel, Jean Louis
AU - Vescovi, Angelo
AU - Pandolfo, Massimo
AU - Koenig, Michel
PY - 1997/10
Y1 - 1997/10
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/6.11.1771
DO - 10.1093/hmg/6.11.1771
M3 - Article
C2 - 9302253
AN - SCOPUS:9844222853
VL - 6
SP - 1771
EP - 1780
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 11
ER -