Frataxin depletion in yeast triggers up-regulation of iron transport systems before affecting iron-sulfur enzyme activities

摘要

The primary function of frataxin, a mitochondrial proteininvolved in iron homeostasis, remains controversial. Using ayeast model of conditional expression of the frataxin homologueYFH1, we analyzed the primary effects of YFH1 depletion.The main conclusion unambiguously points to the upregulationof iron transport systems as a primary effect ofYFH1 down-regulation. We observed that inactivation of aconitase,an iron-sulfur enzyme, occurs long after the iron uptakesystem has been activated. Decreased aconitase activity shouldbe considered part of a group of secondary events promoted byiron overloading, which includes decreased superoxide dismutaseactivity and increased protein carbonyl formation. Impairedmanganese uptake, which contributes to superoxidedismutase deficiency, has also been observed in YFH1-deficientcells. This low manganese content can be attributed tothe down-regulation of the metal ion transporter Smf2. LowSmf2 levels were not observed in AFT1/YFH1 double mutants,indicating that high iron levels could be responsible for theSmf2 decline. In summary, the results presented here indicatethat decreased iron-sulfur enzyme activities in YFH1-deficientcells are the consequence of the oxidative stress conditionssuffered by these cells.