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 patient...

Friedreich ataxia (FA) is a neurodegenerative disease caused by the deficiency of frataxin, mitochondrial protein. In primary cultures dorsal root ganglia neurons, we showed that frataxin depletion resulted in decreased levels calcium exchanger NCLX, neurite degeneration and apoptotic cell death. Here, describe frataxin-deficient neurons display low ferredoxin 1 (FDX1), Fe/S cluster-containing ...

Frataxin is a conserved mitochondrial protein deficient in patients with Friedreich's ataxia. Frataxin has been implicated in control of iron homoeostasis and Fe-S cluster assembly. In yeast or human mitochondria, frataxin interacts with components of the Fe-S cluster synthesis machinery, including the cysteine desulfurase Nfs1, accessory protein Isd11 and scaffold protein Isu. In the present p...

Frataxin is a mitochondrial protein deficient in Friedreich ataxia (FRDA) and which is associated with abnormal intramitochondrial iron handling. We identified the mitochondrial processing peptidase beta (MPPbeta) as a frataxin protein partner using the yeast two-hybrid assay. In in vitro assays, MPPbeta binds frataxin which is cleaved by the reconstituted MPP heterodimer. MPP cleavage of frata...

The most common causative mutation of Friedreich ataxia (FRDA) is the unstable hyperexpansion of an intronic GAA triplet repeat that impairs frataxin transcription. Using real time quantitative PCR, we showed that FRDA patients had residual levels of frataxin mRNA ranging between 13% and 30% and that FRDA carriers had about 40% of that of controls. Asymptomatic carriers also showed reduced frat...

BACKGROUND Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis. METHODOLOGY/PRINCIPAL FINDINGS We present data providing new insights into t...

Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA)--a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin--have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions th...

Frataxin is a nuclear-encoded mitochondrial protein which is deficient in Friedreich's ataxia, a hereditary neurodegenerative disease. Yeast mutants lacking the yeast frataxin homologue (Yfh1p) show iron accumulation in mitochondria and increased sensitivity to oxidative stress, suggesting that frataxin plays a critical role in mitochondrial iron homeostasis and free radical toxicity. Both Yfh1...

Much has been learned about the cellular pathology of Friedreich's ataxia, a recessive neurodegenerative disease resulting from insufficient expression of the mitochondrial protein frataxin. However, the biochemical function of frataxin has remained obscure, hampering attempts at therapeutic intervention. To predict functional interactions of frataxin with other proteins we investigated whether...

BACKGROUND Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the protein frataxin, recently described to be an iron chaperone for the assembly of iron-sulphur clusters in the mitochondria, causing iron accumulation in mitochondria, oxidative stress and cell damage. Searching for compounds that could possibly influence frataxin expression, we found that...