Sensitivity of FRDA Lymphoblasts to Salts of Transition Metal Ions

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease resulting from decreased expression of the nuclear-encoded mitochondrial protein, frataxin. FRDA patients have characteristic iron deposits and dysfunction of mitochondrial enzymes in the heart. Inactivation of the frataxin homologue in yeast causes dysregulation of both mitochondrial iron levels and iron export. Previously, we have observed sensitivity of FRDA fibroblasts to FeCl₃ and hydrogen peroxide, results consistent with the hypothesis that FRDA cells may experience increased Fenton chemistry. To determine whether the sensitivity of FRDA cells to transition metal ions is a general or specific property, we have compared the sensitivity of lymphoblasts from FRDA patients and healthy controls to the transition metal salts CoCl₂, CuSO₄ FeCl₃ FeSO₄, MnCl₂, and ZnCl₂. FRDA lymphoblasts were significantly more sensitive to FeCl₃ and MnCl₂ than control cells. However, there were no significant differences observed in sensitivity to CoCl₂, CuSO₄, FeSO₄ and ZnCl₂ in the concentration ranges studied. Thus, the sensitivity of FRDA lymphoblasts exposed to transition metals appears to be specific, and could be relevant to the pathophysiological mechanism, which is discussed.