title: The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins.
abstract: The genome of the yeast Saccharomyces cerevisiae encodes the essential protein Nar1p that is conserved in virtually all eukaryotes and exhibits striking sequence similarity to bacterial iron-only hydrogenases. A human homologue of Nar1p was shown previously to bind prenylated prelamin A in the nucleus. However, yeast neither exhibits hydrogenase activity nor contains nuclear lamins. Here, we demonstrate that Nar1p is predominantly located in the cytosol and contains two adjacent iron-sulphur (Fe/S) clusters. Assembly of its Fe/S clusters crucially depends on components of the mitochondrial Fe/S cluster biosynthesis apparatus such as the cysteine desulphurase Nfs1p, the ferredoxin Yah1p and the ABC transporter Atm1p. Using functional studies in vivo, we show that Nar1p is required for maturation of cytosolic and nuclear, but not of mitochondrial, Fe/S proteins. Nar1p-depleted cells do not accumulate iron in mitochondria, distinguishing these cells from mutants in components of the mitochondrial Fe/S cluster biosynthesis apparatus. In conclusion, Nar1p represents a crucial, novel component of the emerging cytosolic Fe/S protein assembly machinery that catalyses an essential and ancient process in eukaryotes.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse, Marburg, Germany.
authors.forename: Janneke
authors.initials: J
authors.lastname: Balk
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pierik
authors.forename: Daili J Aguilar
authors.initials: DJ
authors.lastname: Netz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D006864:Hydrogenase / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D007506:Iron-Sulfur Proteins; D029701:Saccharomyces cerevisiae Proteins; D006859:Hydrogen; D007501:Iron; D006864:Hydrogenase; C501975:Nar1 protein, S cerevisiae