Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae.
nifU of nitrogen-fixing bacteria is involved in the synthesis of the Fe-S cluster of nitrogenase. In a synthetic lethal screen with the mitochondrial heat shock protein (HSP)70, SSQ1, we identified a gene of Saccharomyces cerevisiae, NFU1, which encodes a protein with sequence identity to the C-terminal domain of NifU. Two other yeast genes were found to encode proteins related to the N-terminal domain of bacterial NifU. They have been designated ISU1 and ISU2. Isu1, Isu2, and Nfu1 are located in the mitochondrial matrix. ISU genes of yeast carry out an essential function, because a Deltaisu1Deltaisu2 strain is inviable. Growth of Deltanfu1Delta isu1 cells is significantly compromised, allowing assessment of the physiological roles of Nfu and Isu proteins. Mitochondria from Deltanfu1Deltaisu1 cells have decreased activity of several respiratory enzymes that contain Fe-S clusters. As a result, Deltanfu1Deltaisu1 cells grow poorly on carbon sources requiring respiration. Deltanfu1Deltaisu1 cells also accumulate abnormally high levels of iron in their mitochondria, similar to Deltassq1 cells, indicating a role for these proteins in iron metabolism. We suggest that NFU1 and ISU1 gene products play a role in iron homeostasis, perhaps in assembly, insertion, and/or repair of mitochondrial Fe-S clusters. The conservation of these protein domains in many organisms suggests that this role has been conserved throughout evolution.
Schilke
B
B
Department of Biomolecular Chemistry, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Voisine
C
C
Beinert
H
H
Craig
E
E
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D002458:Cell Fractionation; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D005800:Genes, Fungal; D005804:Genes, Lethal; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones / Q000235:genetics*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C121520:ISU1 protein, S cerevisiae; C121521:ISU2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C121524:NFU1 protein, S cerevisiae; C088637:NifU protein, Bacteria; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron