is a protein
that in humans is encoded by the FXN gene
Frataxin is localized to the mitochondrion
. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur cluster
s. It has been proposed to act as either an iron chaperone
or an iron storage protein.
is predominantly expressed
s with a high metabolic rate
(including liver, kidney, brown fat and heart). Mouse
contain a potential N-terminal mitochondrial
targeting sequence, and human
frataxin has been observed to co-localise with a mitochondrial
protein. Furthermore, disruption of the yeast
gene has been shown to result in mitochondria
l dysfunction. Friedreich's ataxia
is thus believed to be a mitochondrial disease
caused by a mutation
in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat in the FXN gene, which encodes the protein frataxin.).
Reduced expression of frataxin is the cause of Friedreich's ataxia
(FRDA), a lethal neurodegenerative disease. The reduction in frataxin gene expression may be attributable from either the silencing of transcription of the frataxin gene because of epigenetic modifications in the chromosomal entity or from the inability of splicing the expanded GAA repeats in the first intron of the pre-mRNA as seen in Bacteria and Human cells or both. The expansion of intron
ic trinucleotide repeat GAA results in Friedreich's ataxia. This expanded repeat causes R-loop formation, and using a repeat-targeted oligonucleotide to disrupt the R-loop can reactivate frataxin expression.
An overexpression of frataxin in Drosophila
has shown an increase in antioxidant capability, resistance to oxidative stress insults and longevity.
Frataxin has been shown to biologically interact
with the enzyme PMPCB