Frataxin Human

Frataxin, also known as FXN, is a mitochondrial protein that plays a crucial role in iron metabolism. It is encoded by the FXN gene and is involved in the biosynthesis of iron-sulfur (Fe-S) clusters and heme, which are essential for various cellular processes . Deficiency in frataxin leads to Friedreich’s ataxia (FRDA), a progressive neurodegenerative disorder characterized by gait and limb ataxia, cardiomyopathy, and diabetes .

Frataxin is synthesized as a precursor polypeptide consisting of 210 amino acids. It is directed to the mitochondrial matrix, where it undergoes proteolytic cleavage to form the mature protein . The mature form of frataxin is involved in iron storage and acts as an iron chaperone, preventing mitochondrial damage and reactive oxygen species production . It is essential for the formation of Fe-S clusters, which are critical for mitochondrial function and cellular viability .

Friedreich’s ataxia is caused by mutations in the FXN gene, leading to a significant reduction in frataxin levels. The most common mutation is a GAA trinucleotide repeat expansion within the first intron of the FXN gene . This mutation interferes with transcriptional elongation and leads to heterochromatin formation, resulting in decreased frataxin expression . The deficiency in frataxin disrupts iron metabolism, leading to iron accumulation in mitochondria, impaired Fe-S cluster biosynthesis, and increased oxidative stress .

Recombinant human frataxin is produced using genetic engineering techniques to express the human FXN gene in various host systems, such as bacteria or yeast . This recombinant protein is used in research to study the biochemical function of frataxin and to develop potential therapeutic approaches for FRDA . The availability of recombinant human frataxin has facilitated the investigation of its role in iron metabolism and its potential as a therapeutic target .