title: Mitochondrial functioning of constitutive iron uptake mutations in Cryptococcus neoformans.
abstract: Randomly obtained, constitutive plasma membrane ferric reductase/ferrous uptake mutants of Cryptococcus neoformans were mapped to four distinct loci by meiotic analysis. One of those loci, FRR1 , was previously found homologous to MRS3 and MRS4 of Saccharomyces cerevisiae , which determine proteins involved in mitochondrial transport of iron. We were able to complement, clone, sequence and thereby identify two of the three remaining constitutive uptake loci. FRR3 was found to be homologous to ISU1 and ISU2 of S. cerevisiae, which form mitochondrial iron-sulfur complexes; FRR4 was found to be homologous to YFH1, the yeast frataxin homologue, which also participates in iron-sulfur cluster biogenesis. Because of the constitutive iron uptake seen in these mutants, mitochondria appear to have a central role in the cellular iron economy; moreover, as judged by our mutational statistics, the genetic machinery for mitochondrial iron accumulation may be more complex than that of the cytoplasm.
authors.affiliation: Research Service, McGuire Veterans Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23249, USA. eric.jacobson2@med.va.gov
authors.forename: Eric S
authors.initials: ES
authors.lastname: Jacobson
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Troy
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Nyhus
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D038181:FMN Reductase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D027682:Cation Transport Proteins; D004271:DNA, Fungal; D007501:Iron; D038181:FMN Reductase; C023903:ferric citrate iron reductase