Uncovering the function of a conserved site in eukaryotic frataxins

This project aims to identify all functions of frataxin. Dr. Tamarit and his group identified the presence of a group of amino acids highly conserved in frataxins from different organisms.  This group of amino acids, called cluster 3, is, however, not conserved in bacteria. This led to the hypothesis that these amino acids in eukaryotes could be performing a crucial role, gained during evolution, in frataxin function. The working hypothesis is that these residues may be involved in frataxin antioxidant properties or in ferroxidase activity, activities not observed in bacterial frataxins. To test this hypothesis, the investigators will generate mutant frataxins in which amino acids from cluster 3 will be substituted by the residues found in bacteria and test their function. The results from the proposed project may open new perspectives for treatment, as drugs mimicking the function of complex 3 could be developed. They may also contribute to understanding the mechanism by which frataxin overexpression is toxic and to design strategies to attenuate such toxicity.