title: A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins.
abstract: Iron-sulfur (Fe/S) cluster-containing proteins catalyze a number of electron transfer and metabolic reactions. The components and molecular mechanisms involved in the assembly of the Fe/S clusters have been identified only partially. In eukaryotes, mitochondria have been proposed to execute a crucial task in the generation of intramitochondrial and extramitochondrial Fe/S proteins. Herein, we identify the essential ferredoxin Yah1p of Saccharomyces cerevisiae mitochondria as a central component of the Fe/S protein biosynthesis machinery. Depletion of Yah1p by regulated gene expression resulted in a 30-fold accumulation of iron within mitochondria, similar to what has been reported for other components involved in Fe/S protein biogenesis. Yah1p was shown to be required for the assembly of Fe/S proteins both inside mitochondria and in the cytosol. Apparently, at least one of the steps of Fe/S cluster biogenesis within mitochondria requires reduction by ferredoxin. Our findings lend support to the idea of a primary function of mitochondria in the biosynthesis of Fe/S proteins outside the organelle. To our knowledge, Yah1p is the first member of the ferredoxin family for which a function in Fe/S cluster formation has been established. A similar role may be predicted for the bacterial homologs that are encoded within iron-sulfur cluster assembly (isc) operons of prokaryotes.
authors.affiliation: Institut für Zytobiologie und Zytopathologie der Philipps-Universität Marburg, Robert-Koch-Strasse 5, 35033 Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Lange
authors.forename: A
authors.initials: A
authors.lastname: Kaut
authors.forename: G
authors.initials: G
authors.lastname: Kispal
authors.forename: R
authors.initials: R
authors.lastname: Lill
mesh_terms: D000325:Adrenodoxin; D000595:Amino Acid Sequence; D001059:Apoproteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry; D003470:Culture Media / Q000494:pharmacology; D005288:Ferredoxins / Q000737:chemistry / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; D003470:Culture Media; D005288:Ferredoxins; D005656:Fungal Proteins; D007506:Iron-Sulfur Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C120375:YAH1 protein, S cerevisiae; D000325:Adrenodoxin