Definition: Frataxin (FXN) has an essential role in mitochondrial iron homeostasis and functions in regulating mitochondrial iron transport and respiration.

Frataxin (FXN) is a small protein, localized to the mitochondrion.

The function of frataxin (FXN) is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters (iron-sulfur cluster biogenesis).

Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.

Etiology

Deficiency of frataxin (FXN) is the cause of Friedrich ataxia.

The expansion of intronic trinucleotide repeat GAA in FXN gene results in Friedreich ataxia.

Friedreich ataxia can therefore be considered as an OXPHOS homeostasis defect.

Pathogenesis

Mitochondria obtained from heart biopsies of Friedreich ataxia patients have disclosed specific defects in the citric-acid cycle enzyme aconitase, and complex I-III activities.

See also

 iron-sulfur clusters

• iron-sulfur cluster biogenesis

Reviews

 Shoubridge EA. Nuclear genetic defects of oxidative phosphorylation. Hum Mol Genet. 2001 Oct 1;10(20):2277-84. PMID: 11673411

 Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet. 2001 May;2(5):342-52. PMID: 11331900

 Rotig A, Sidi D, Munnich A, Rustin P. Molecular insights into Friedreich’s ataxia and antioxidant-based therapies. Trends Mol Med. 2002 May;8(5):221-4. PMID: 12067631

 Puccio H, Koenig M. Recent advances in the molecular pathogenesis of Friedreich ataxia. Hum Mol Genet. 2000 Apr 12;9(6):887-92. PMID: 10767311

References

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