@article{5f5ef7c33beb4e8bb130cfff1dbd05fb,
title = "Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes",
abstract = "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.",
author = "Victoria Campuzano and Laura Montermini and Yves Lutz and Lidia Cova and Colette Hindelang and Sarn Jiralerspong and Yvon Trottier and Kish, {Stephen J.} and Baptiste Faucheux and Paul Trouillas and Authier, {Fran{\c c}ois J.} and Alexandra D{\"u}rr and Mandel, {Jean Louis} and Angelo Vescovi and Massimo Pandolfo and Michel Koenig",
note = "Funding Information: We wish to thank Dr A.Lomb{\`e}s for the anti-cytochrome c oxidase antibody, Dr R.Gatti for lymphoblastoid cell lines and Drs T.Gibson and F.Foury for sharing unpublished results. Thanks are due to Dr Coss{\'e}e for analysis of patients and discussions and to H.Koutnikova for discussions. We are grateful to L.Reutenauer, S.Vicaire, F.Ruffenach, N.Jung, F.Cottin and V.Schultz for their technical assistance. This work was supported by funds from the Association Fran{\c c}aise contre les Myopathies (AFM), CNRS, INSERM and the Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur et de la Recherche (M.K.) and by grants from the National Institutes of Health (NS34192) and the Muscular Dystrophy Association, USA (M.P.). V.C. is the recipient of a fellowship from the EEC and L.M. is the recipient of a fellowship from the Medical Research Council of Canada. Y.T. is the recipient of a fellowship from the Hereditary Disease Foundation (USA).",
year = "1997",
month = oct,
doi = "10.1093/hmg/6.11.1771",
language = "English (US)",
volume = "6",
pages = "1771--1780",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "11",
}