Identification of iron-binding regions and the crystal structure of frataxin, in flies

What is it about?

The protein frataxin is a key component of the mitochondrial iron-sulfur cluster assembly (ISC) pathway. Within the ISC, frataxin works with five other proteins to complete the biosynthesis of iron-sulfur clusters; cofactors that are essential in biochemical pathways. A disruption within the ISC pathway, due to a lack of frataxin, can cause a genetic disorder called Friedreich's Ataxia. Here, we study the structure of frataxin, as it relates to its function within the ISC pathway, to better understand its role in iron-sulfur cluster bioassembly. Previous reports have investigated frataxin of human and yeast models, however frataxin of flies has shown to be more stable.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

Friedreich’s Ataxia (FRDA) is the most prevalent hereditary disease linked to failed iron-sulfur (Fe-S) cluster biosynthesis. FRDA is a human autosomal recessive genetic disorder caused by a trinucleotide expansion within the frataxin gene (FXN), which codes for the frataxin protein, FXN. The trinucleotide repeat results in an under expression of frataxin. This deficiency pathologically presents as mitochondrial iron overload, increased reactive oxygen species production, and a disruption in Fe-S cluster biosynthesis. Combined, these phenotypes are cytotoxic in metabolic tissues including the dorsal root ganglia and cardiomyocytes. FRDA presents in early adolescence as seen by positive ataxia, poor muscle coordination, and dysarthria. The protein frataxin is a key component in the mitochondrial iron-sulfur cluster bioassembly (ISC) pathway, where it serves as a modulator for cysteine desulfurase, and likely iron delivery to the scaffold.

Perspectives