Frataxin depletion in yeast triggers up-regulation of iron transport systems before affecting iron-sulfur enzyme activities
Moreno Cermeño, Armando J.
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The primary function of frataxin, a mitochondrial protein involved in iron homeostasis, remains controversial. Using a yeast model of conditional expression of the frataxin homologue YFH1, we analyzed the primary effects of YFH1 depletion. The main conclusion unambiguously points to the upregulation of
iron transport systems as a primary effect of YFH1 down-regulation. We observed that inactivation of aconitase, an iron-sulfur enzyme, occurs long after the iron uptake system has been activated. Decreased aconitase activity should be considered part of a group of secondary events promoted by iron overloading, which includes decreased superoxide dismutase activity and increased protein carbonyl formation. Impaired manganese uptake, which contributes to superoxide dismutase deficiency, has also been observed in YFH1-deficient cells. This low manganese content can be attributed to the down-regulation of the metal ion transporter Smf2. Low Smf2 levels were not observed in AFT1/YFH1 double mutants, indicating that high iron levels could be responsible for the Smf2 decline. In summary, the results presented here indicate that decreased iron-sulfur enzyme activities in YFH1-deficient cells are the consequence of the oxidative stress conditions suffered by these cells.
Is part ofThe Journal of Biological Chemistry, 2010, vol. 285, núm. 53, p. 41653-41664
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Yeast frataxin mutants display decreased superoxide dismutase activity crucial to promote protein oxidative damage Irazusta, Verónica Patricia; Obis Monné, Èlia; Moreno Cermeño, Armando J.; Cabiscol Català, Elisa; Ros Salvador, Joaquim; Tamarit Sumalla, Jordi (Elsevier, 2010)Iron overload is involved in several pathological conditions, including Friedreich ataxia, a disease caused by decreased expression of the mitochondrial protein frataxin. In a previous study, we identified 14 proteins ...
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