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Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function.


ABSTRACT: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by GAA triplet expansions or point mutations in the FXN gene on chromosome 9q13. The gene product called frataxin, a mitochondrial protein that is severely reduced in FRDA patients, leads to mitochondrial iron accumulation, Fe-S cluster deficiency and oxidative damage. The tissue specificity of this mitochondrial disease is complex and poorly understood. While frataxin is ubiquitously expressed, the cellular phenotype is most severe in neurons and cardiomyocytes. Here, we conducted comprehensive proteomic, metabolic and functional studies to determine whether subclinical abnormalities exist in mitochondria of blood cells from FRDA patients. Frataxin protein levels were significantly decreased in platelets and peripheral blood mononuclear cells from FRDA patients. Furthermore, the most significant differences associated with frataxin deficiency in FRDA blood cell mitochondria were the decrease of two mitochondrial heat shock proteins. We did not observe profound changes in frataxin-targeted mitochondrial proteins or mitochondrial functions or an increase of apoptosis in peripheral blood cells, suggesting that functional defects in these mitochondria are not readily apparent under resting conditions in these cells.

SUBMITTER: Selak MA 

PROVIDER: S-EPMC4419809 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function.

Selak Mary A MA   Lyver Elise E   Micklow Elizabeth E   Deutsch Eric C EC   Onder Ozlem O   Selamoglu Nur N   Yager Claire C   Knight Simon S   Carroll Martin M   Daldal Fevzi F   Dancis Andrew A   Lynch David R DR   Sarry Jean-Emmanuel JE  

Mitochondrion 20101213 2


Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by GAA triplet expansions or point mutations in the FXN gene on chromosome 9q13. The gene product called frataxin, a mitochondrial protein that is severely reduced in FRDA patients, leads to mitochondrial iron accumulation, Fe-S cluster deficiency and oxidative damage. The tissue specificity of this mitochondrial disease is complex and poorly understood. While frataxin is ubiquitously expressed, the cellular phe  ...[more]

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