Part 2/2 of Dr. S. Adinolfi's presentation on the frataxin function

Dr. S. Adinolfi's presentation given on September 25th 2009 at the euro-Ataxia scientific meeting of Valladolid, Spain, organized by FEDAES: "Frataxin is the gatekeeper of Fe-S cluster formation".
Dr. Salvatore Adinolfi, Annalisa Pastore's team.
Iron-sulfur cluster formation is an essential and yet poorly understood metabolic pathway common to all living organisms. Frataxin, an essential and highly conserved mitochondrial protein whose reduced expression causes Friedreich'a Ataxia (FRDA or FA) in humans, has been described as an iron chaperone which provides iron in iron-sulfur cluster assembly. We have tested this hypothesis using a bacterial model and different biochemical and molecular biology techniques. We could show that CyaY, the bacterial orthologue of frataxin, intervenes in iron-sulfur (Fe-S) cluster assembly not simply as an iron donor. Through binding to the desulfurase IscS with a 1:1 stoichiometry and micromolar affinity, frataxin acts as an iron concentration dependent inhibitor of cluster formation. This suggested that frataxin is an iron sensor which acts as the gate keeper for Fe-S cluster formation and fine tunes the quantity of Fe-S clusters formed to the concentration and/or possibly the distribution of the available acceptors. Our observations provide a new perspective for understanding FRDA and a mechanistic model which rationalizes the available knowledge.
Source: euro-Ataxia meeting 2009/FEDAES

Category:

Science & Technology

Tags:

• frataxin
• ataxia
• euro-Ataxia
• meeting
• FRDA
• Friedreich's
• Ataxia
• atassia
• di
• Friedreich
• FA
• ataxie
• Adinolfi
• Pastore