Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron−sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich’s ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe−S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron−sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway.

Molecular Details of the Yeast Frataxin-Isu1 Interaction during Mitochondrial Fe-S Cluster Assembly

Reactive oxygen species (ROS) actively contribute to the development of a number of human diseases including ischemia. In response to oxidative stress, frataxin has a significant ability to improve cell survival though its biological function is unclear in relation to ischemia. To explore frataxin's role in protecting against ischemic cell death, we constructed PEP-1-Frataxin cell-permeable fusion protein.

Protective effects of transduced PEP-1-Frataxin protein on oxidative stress-induced neuronal cell death

Friedreich ataxia (FRDA) is the most common hereditary ataxia that is caused mainly by an unstable GAA trinucleotide expansion in the first intron of the frataxin gene. Molecular tests for FRDA diagnosis and carrier detection include polymerase chain reaction (PCR) for the GAA expansion, triplet repeat primed PCR (TP-PCR), and/or Southern blotting. TP-PCR is a method developed to detect trinucleotide expansions successfully applied to FRDA diagnosis. In our laboratory, we have included a PCR for the GAA expansion using fluorescent primers polymerase chain reaction (F-PCR) to identify normal heterozygous and affected individuals unambiguously.

Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction

Friedreich's ataxia (FRDA) and ataxia with oculomotor apraxia type 2 (AOA2) are the two most frequent forms of autosomal recessive cerebellar ataxias. However, brain metabolism in these disorders is poorly characterized and biomarkers of the disease progression are lacking. We aimed at assessing the neurochemical profile of the pons, the cerebellar hemisphere and the vermis in patients with FRDA and AOA2 to identify potential biomarkers of these diseases.

1H MR Spectroscopy in Friedreich's Ataxia and Ataxia with Oculomotor Apraxia Type 2