title: Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).
abstract: Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Δyfh1) accumulate iron in the mitochondria in the form of nanoparticles of ferric phosphate. The phosphate content of Δyfh1 mitochondria was higher than that of wild-type mitochondria, but the proportion of mitochondrial phosphate that was soluble was much lower in Δyfh1 cells. The rates of phosphate and iron uptake in vitro by isolated mitochondria were higher for Δyfh1 than wild-type mitochondria, and a significant proportion of the phosphate and iron rapidly became insoluble in the mitochondrial matrix, suggesting co-precipitation of these species after oxidation of iron by oxygen. Increasing the amount of phosphate in the medium decreased the amount of iron accumulated by Δyfh1 cells and improved their growth in an iron-dependent manner, and this effect was mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier, MIR1, slightly increased the concentration of soluble mitochondrial phosphate and significantly improved various mitochondrial functions (cytochromes, [Fe-S] clusters, and respiration) in Δyfh1 cells. We conclude that in Δyfh1 cells, soluble phosphate is limiting, due to its co-precipitation with iron.
authors.affiliation: Institut Jacques Monod, CNRS-University Paris Diderot 75205 Paris cedex 13, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Seguin
authors.forename: Renata
authors.initials: R
authors.lastname: Santos
authors.forename: Debkumar
authors.initials: D
authors.lastname: Pain
authors.forename: Andrew
authors.initials: A
authors.lastname: Dancis
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Camadro
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lesuisse
mesh_terms: D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D028061:Phosphate Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000096923:Frataxin
chemical_list: D007501:Iron; D033862:Iron-Binding Proteins; D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin; C435723:MIR1 protein, S cerevisiae