Frataxin (FXN) (FXN)

Frataxin (FXN) is a nuclear-encoded mitochondrial protein that plays a critical role in cellular iron metabolism and the biogenesis of iron-sulfur (Fe-S) clusters (UniProt Q16595). It functions as an iron chaperone, facilitating the transfer of iron to the ISCU scaffold protein during the assembly of Fe-S clusters, which are essential for mitochondrial respiration and DNA repair (PubMed: 29107506). A deficiency in frataxin, primarily caused by a GAA trinucleotide repeat expansion in the first intron of the FXN gene, results in Friedreich's ataxia (FRDA), a multisystem disorder characterized by progressive ataxia, sensory loss, and hypertrophic cardiomyopathy (NIH: GARD). Therapeutic approaches focus on restoring frataxin levels through gene therapy, protein replacement, or small molecules that increase FXN expression or stabilize the protein (PubMed: 31515460). Omaveloxolone, an Nrf2 activator, is the first FDA-approved treatment for FRDA, aimed at improving mitochondrial function and reducing oxidative stress (FDA: 2023).

Other names

FXNFRDAFAX25CshFriedreich ataxia protein

Therapeutic strategies focus on increasing frataxin protein levels through gene therapy, protein replacement, or pharmacological induction of the FXN gene, as well as mitigating mitochondrial dysfunction and oxidative stress caused by frataxin deficiency (PubMed: 31515460).