February 2013

The role of frataxin in the neurological disorder Friedreich ataxia

Elena Hidalgo 
Elena Hidalgo

Friedreich ataxia is a rare genetic autosomal recessive disease that damages the nervous system and causes movement problems. The disease is named after the German physician Nikolaus Friedreich, who was the first to describe it in the 1860s. It usually begins in childhood, typically between the ages of 5 and 15, and worsens with age. The condition causes the degeneration of nerve tissue in the spinal cord, especially in the sensory neurons that direct muscle movement of the arms and legs.

The disease involves deficiencies in the protein called frataxin. The protein has homologues in both eukaryotes and prokaryotes, but its function is still unresolved. In a recent “Paper of the Week” in The Journal of Biological Chemistry, a team led by Elena Hidalgo at the Universitat Pompeu Fabra in Spain identified a frataxin homologue in the mitochondria of fission yeast. The investigators found that cells missing the gene for the protein were sensitive to growth under aerobic conditions, had increased levels of total iron, showed signs of oxidative stress and consumed less oxygen compared to wild-type cells. These signs closely mimic the problems associated with reduced frataxin levels in cells from Friedreich ataxia patients. Proteomic analysis showed that when cells were missing the frataxin homologue iron in the cytosol was less readily available, causing the activation of a regulator of the iron-starvation gene expression program.

The data suggest that the frataxin homologue is important for iron and reactive oxygen species homeostasis. The investigators say their strain of fission yeast missing the frataxin homologue will make a new model for studying the molecular basis for Friedreich ataxia.

To hear a podcast discussion about this paper with Hidalgo, go to www.jbc.org/site/podcast/2012 or find the JBC podcast site on iTunes.

Rajendrani MukhopadhyayRajendrani Mukhopadhyay (rmukhopadhyay@asbmb.org) is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter (www.twitter.com/rajmukhop), and read her ASBMB Today blog, Wild Types.

found= true2169