Frataxin
Encyclopedia
Frataxin 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.
Frataxin mRNA is predominantly expressed
in tissue
s with a high metabolic
rate
(including liver, kidney, brown fat and heart). Mouse and yeast
frataxin homologues
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 mitochondrial 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).
(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 modifciations 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.
An overexpression of frataxin in Drosophila
has shown an increase in antioxidant capability, resistance to oxidative stress insults and longevity.
with PMPCB
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FXN gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Frataxin is localized to the mitochondrion
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur cluster
Iron-sulfur cluster
For biological Fe-S clusters, see iron-sulfur proteins.Iron-sulfur clusters are ensembles of iron and sulfide centres. Fe-S clusters are most often discussed in the context of the biological role for iron-sulfur proteins. Many Fe-S clusters are known in the area of organometallic chemistry and as...
s. It has been proposed to act as either an iron chaperone or an iron storage protein.
Frataxin mRNA is predominantly expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s with a high metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
rate
Rate
In mathematics, a rate is a ratio between two measurements, often with different units. If the unit or quantity in respect of which something is changing is not specified, usually the rate is per unit time. However, a rate of change can be specified per unit time, or per unit of length or mass or...
(including liver, kidney, brown fat and heart). Mouse and yeast
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
frataxin homologues
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
contain a potential N-terminal mitochondrial
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia
Friedreich's ataxia
Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system, resulting in symptoms ranging from gait disturbance to speech problems; it can also lead to heart disease and diabetes....
is thus believed to be a mitochondrial disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
caused by a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat).
Clinical significance
Reduced expression of frataxin is the cause of Friedreich's ataxiaFriedreich's ataxia
Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system, resulting in symptoms ranging from gait disturbance to speech problems; it can also lead to heart disease and diabetes....
(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 modifciations 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
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
ic trinucleotide repeat GAA results in Friedreich's ataxia.
An overexpression of frataxin in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
has shown an increase in antioxidant capability, resistance to oxidative stress insults and longevity.
Interactions
Frataxin has been shown to biologically interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PMPCB
PMPCB
Mitochondrial-processing peptidase subunit beta is an enzyme that in humans is encoded by the PMPCB gene.-Further reading:...
.