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Journal of Neurology

, Volume 256, Supplement 1, pp 9–17 | Cite as

The pathogenesis of Friedreich ataxia and the structure and function of frataxin

  • Massimo Pandolfo
  • Annalisa Pastore
Article

Abstract

Understanding the role of frataxin in mitochondria is key to an understanding of the pathogenesis of Friedreich ataxia. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, which include oxidative stress, deficit of iron-sulphur clusters, and defects in heme synthesis, sulfur amino acid and energy metabolism, stress response, and mitochondrial function. Structural studies carried out on different orthologues have shown that the frataxin fold consists of a flexible N-terminal region present only in eukaryotes and in a highly conserved C-terminal globular domain. Frataxins bind iron directly but with very unusual properties: iron coordination is achieved solely by glutamates and aspartates exposed on the protein surface. It has been suggested that frataxin function is that of a ferritin-like protein, an iron chaperone of the ironsulphur cluster machinery and heme metabolism and/or a controller of cellular oxidative stress. To understand FRDA pathogenesis and to design novel therapeutic strategies, we must first precisely identify the cellular role of frataxin.

Key words

mitochondria iron metabolism oxidative stress 

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Copyright information

© Steinkopff-Verlag 2009

Authors and Affiliations

  1. 1.Service de NeurologieHôpital Erasme – Université Libre de BruxellesBrusselsBelgium
  2. 2.The National Institute for Medical ResearchLondonUK

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