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Title: Novel frataxin isoforms may contribute to the pathological mechanism of friedreich ataxia
Authors: Xia, H
Cao, Y
Dai, X
Marelja, Z
Zhou, D
Mo, R
Al-Mahdawi, S
Pook, MA
Leimkühler, S
Rouault, TA
Li, K
Issue Date: 2012
Publisher: Public Library of Science
Citation: PLoS ONE, 7(10): e47847, Oct 2012
Abstract: Friedreich ataxia (FRDA) is an inherited neurodegenerative disease caused by frataxin (FXN) deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III), which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.
Description: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
ISSN: 1932-6203
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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