title: Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells.
abstract: Iron-sulfur (Fe-S) clusters are cofactors found in many proteins that have important redox, catalytic or regulatory functions. In mammalian cells, almost all known Fe-S proteins are found in the mitochondria, but at least one is found in the cytosol. Here we report cloning of the human homologs to IscU and NifU, iron-binding proteins that play a critical role in Fe-S cluster assembly in bacteria. In human cells, alternative splicing of a common pre-mRNA results in synthesis of two proteins that differ at the N-terminus and localize either to the cytosol (IscU1) or to the mitochondria (IscU2). Biochemical analyses demonstrate that IscU proteins specifically associate with IscS, a cysteine desulfurase that is proposed to sequester inorganic sulfur for Fe-S cluster assembly. Protein complexes containing IscU and IscS can be found in the mitochondria as well as in the cytosol, implying that Fe-S cluster assembly takes place in multiple subcellular compartments in mammalian cells. The possible roles of the IscU proteins in mammalian cells and the potential implications of compartmentalization of Fe-S cluster assembly are discussed.
authors.affiliation: National Institute of Child Health and Human Development, Cell Biology and Metabolism Branch, Bethesda, MD 20892, USA. trou@helix.nih.gov
authors.forename: W H
authors.initials: WH
authors.lastname: Tong
authors.forename: T
authors.initials: T
authors.lastname: Rouault
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D013437:Carbon-Sulfur Lyases / Q000737:chemistry / Q000378:metabolism; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000235:genetics; D029968:Escherichia coli Proteins; D015870:Gene Expression; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; C411665:IscU protein, E coli; C088637:NifU protein, Bacteria; D004247:DNA; D013437:Carbon-Sulfur Lyases; C080546:cysteine desulfurase