Iron Accumulated in Mitochondria of a YFH1 - Mutant of the Yeast Saccharomyces cerevisiae Corresponds to Inorganic Ferric Phosphate

The YFH1 gene is the yeast homologue of the human FRDA gene encoding a protein named frataxin. Mutations of the frataxin gene lead to a decreased frataxin expression causing Friedreich’s ataxia, the most common autosomal recessive neurodegenerative disease of Caucasians [1,2]. A defect in the yeast frataxin homologue leads to several S. cerevisiae phenotypes. Iron uptake is considerably higher compared to wildtype cells, with most of the iron being found in the mitochondria [3]. These cells exhibit defective respiration [3,5,7,8], unstable mitochondrial DNA and hypersensitivity to oxidative stress [3-5]. The assembly of Fe-S centers is impaired and the cells display drastically decreased cytochrome concentrations [4]. One major goal of our project was to uncover the role of yfh1 in mitochondrial iron metabolism of yeast and in particular, to identify the major mitochondrial iron components. For this purpose we analysed mitochondria of wild-type Saccharomyces and of a yfh1 mutant strain by means of in situ Mössbauer spectroscopy [9], EXAFS and biochemical methods.