Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells

EMBO J. 2000 Nov 1;19(21):5692-700. doi: 10.1093/emboj/19.21.5692.


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.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Sequence
  • COS Cells
  • Carbon-Sulfur Lyases / chemistry
  • Carbon-Sulfur Lyases / metabolism
  • Cell Compartmentation
  • Cloning, Molecular
  • Cytosol / metabolism
  • DNA / genetics
  • Escherichia coli Proteins*
  • Gene Expression
  • Humans
  • Iron-Sulfur Proteins / chemistry*
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism*
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Transfection


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Iron-Sulfur Proteins
  • IscU protein, E coli
  • NifU protein, Bacteria
  • DNA
  • Carbon-Sulfur Lyases
  • cysteine desulfurase

Associated data

  • GENBANK/AY009127
  • GENBANK/AY009128