Skip to main content

Iron in yeast: Mechanisms involved in homeostasis

Part of the Topics in Current Genetics book series (TCG,volume 14)

Abstract

Iron homeostasis results from matching iron uptake to cell growth and division in the context of the overall cell requirement for iron. Fungi achieve this balance by transcriptional regulation of the genes that encode iron uptake activities; post-transcriptional regulation of the synthesis of proteins that use iron; and storage and recycling of iron to meet short-term needs in times of iron deprivation. In the Fungal Kingdom, both repression and activation mechanisms of transcriptional regulation have been elucidated; both mechanisms rely on transcription factors that directly or indirectly are regulated by cell iron status. Among fungi, however, one or the other transcriptional regulatory mechanism is used by a given organism but not both. In contrast, of those fungi examined in detail, all employ at least two of the four iron uptake mechanisms characterized in fungi in general: siderophore iron uptake; direct ferrous iron permeation; coupled ferroxidase/permease uptake; and heme/hemin uptake. All of these pathways rely on the activity of a metalloreductase enzyme at some point. The yeast vacuole serves as iron store while the mitochondrion, as the site of heme and Fe-S cluster biosynthesis, is the primary end-user of cell iron. The recycling of iron from both organelles plays a role in the maintenance of homeostasis both in terms of iron utilization and regulation of iron uptake.

Keywords

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.00
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • 1. Ali A, Zhang Q, Dai J, Huang X (2003) Calcein as a fluorescent iron chemosensor for the determination of low molecular weight iron in biological fluids. Biometals 16:285-293

    PubMed  CAS  Google Scholar 

  • 2. Ardon O, Bussey H, Philpott C, Ward DM, Davis-Kaplan S, Verroneau S, Jiang B, Kaplan J (2001) Identification of a Candida albicans ferrichrome transporter and its charac-terization by expression in Saccharomyces cerevisiae. J Biol Chem 276:43049-43055

    PubMed  CAS  Google Scholar 

  • 3. Ardon O, Nudelman R, Caris C, Libman J, Shanzer A, Chen Y, Hadar Y (1998) Iron uptake in Ustilago maydis: tracking the iron path. J Bacteriol 180:2021-2026

    PubMed  CAS  PubMed Central  Google Scholar 

  • 4. Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J (1994) The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for fer-rous iron uptake. Cell 76:403-410

    PubMed  CAS  Google Scholar 

  • 5. Askwith C, Kaplan J (1997) An oxidase-permease-based iron transport system in Schizosaccharomyces pombe and its expression in Saccharomyces cerevisiae. J Biol Chem 272:401-405

    PubMed  CAS  Google Scholar 

  • 6. Askwith C, Kaplan J (1998) Iron and copper transport in yeast and its relevance to human disease. Trends Biochem Sci 23:135-138

    PubMed  CAS  Google Scholar 

  • 7. Balk J, Pierik AJ, Netz DJ, Muhlenhoff U, Lill R (2004) The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins. EMBO J 23:2105-2115

    PubMed  CAS  PubMed Central  Google Scholar 

  • 8. Bard M, Bruner DA, Pierson CA, Lees ND, Biermann B, Frye L, Koegel C, Barbuch R (1996) Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding C-4 sterol methyl oxidase. Proc Natl Acad Sci USA 93:186-190

    PubMed  CAS  PubMed Central  Google Scholar 

  • 9. Bode HP, Dumschat M, Garotti S, Fuhrmann GF (1995) Iron sequestration by the yeast vacuole. A study with vacuolar mutants of Saccharomyces cerevisiae. Eur J Biochem 228:337-342

    PubMed  CAS  Google Scholar 

  • 10. Boukhalfa H, Crumbliss AL (2002) Chemical aspects of siderophore mediated iron trans-port. Biometals 15:325-339

    PubMed  CAS  Google Scholar 

  • 11. Broadwater JA, Haas JA, Fox BG (1998) The fundamental, versatile role of diiron enzymes in lipid metabolism. Fett/Lipid 100:103-113

    Google Scholar 

  • 12. Buchanan SK, Smith BS, Venkatramani L, Xia D, Esser L, Palnitkar M, Chakraborty R, van der Helm D, Deisenhofer J (1999) Crystal structure of the outer membrane active transporter FepA from Escherichia coli. Nat Struct Biol 6:56-63

    PubMed  CAS  Google Scholar 

  • 13. Bulteau AL, O'Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI (2004) Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305:242-245

    PubMed  CAS  Google Scholar 

  • 14. Casas C, Aldea M, Espinet C, Gallego C, Gil R, Herrero E (1997) The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae. Yeast 13:621-637

    PubMed  CAS  Google Scholar 

  • 15. Chen OS, Crisp RJ, Valachovic M, Bard M, Winge DR, Kaplan J (2004) Transcription of the yeast iron regulon does not respond directly to iron but rather to iron-sulfur cluster biosynthesis. J Biol Chem 279:29513-29518

    PubMed  CAS  Google Scholar 

  • 16. Chen OS, Kaplan J (2000) CCC1 suppresses mitochondrial damage in the yeast model of Friedreich's ataxia by limiting mitochondrial iron accumulation. J Biol Chem 275:7626-7632

    PubMed  CAS  Google Scholar 

  • 17. Clarke TE, Braun V, Winkelmann G, Tari LW, Vogel HJ (2002) X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin. J Biol Chem 277:13966-13972

    PubMed  CAS  Google Scholar 

  • 18. Claros MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241:779-786

    PubMed  CAS  Google Scholar 

  • 19. Crisp RJ, Pollington A, Galea C, Jaron S, Yamaguchi-Iwai Y, Kaplan J (2003) Inhibition of heme biosynthesis prevents transcription of iron uptake genes in yeast. J Biol Chem 278:45499-45506

    PubMed  CAS  Google Scholar 

  • 20. Dailey HA (2002) Terminal steps of haem biosynthesis. Biochem Soc Trans 30:590-595

    PubMed  CAS  Google Scholar 

  • 21. Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP, Wang BC (2000) Ferro-chelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters. Cell Mol Life Sci 57:1909-1926

    PubMed  CAS  Google Scholar 

  • 22. Dailey HA, Finnegan MG, Johnson MK (1994) Human ferrochelatase is an iron-sulfur pro-tein. Biochemistry 33:403-407

    PubMed  CAS  Google Scholar 

  • 23. Dancis A, Roman DG, Anderson GJ, Hinnebusch AG, Klausner RD (1992) Ferric reduc-tase of Saccharomyces cerevisiae: Molecular characterization, role in iron uptake and transcriptional control by iron. Proc Natl Acad Sci USA 89:3869-3873

    PubMed  CAS  PubMed Central  Google Scholar 

  • 24. Davie JK, Edmondson DG, Coco CB, Dent SY (2003) Tup1-Ssn6 interacts with multiple class I histone deacetylases in vivo. J Biol Chem 278:50158-50162

    PubMed  CAS  Google Scholar 

  • 25. Davis-Kaplan SR, Askwith CC, Bengtzen AC, Radisky D, Kaplan J (1998) Chloride is an allosteric effector of copper assembly for the yeast multicopper oxidase Fet3p: an un-expected role for intracellular chloride channels. Proc Natl Acad Sci USA 95:13641-13645

    PubMed  CAS  PubMed Central  Google Scholar 

  • 26. De Luca NG, Wood PM (2000) Iron uptake by fungi: contrasted mechanisms with internal or external reduction. Adv Micro Physiol 43:39-74

    Google Scholar 

  • 27. de Silva DM, Askwith CC, Eide D, Kaplan J (1995) The FET3 gene product required for high affinity iron transport in yeast is a cell surface ferroxidase. J Biol Chem 270:1098-1101

    Google Scholar 

  • 28. Diaz AR, Mansilla MC, Vila AJ, de Mendoza D (2002) Membrane topology of the acyl-lipid desaturase from Bacillus subtilis. J Biol Chem 277:48099-48106

    PubMed  CAS  Google Scholar 

  • 29. Dix D, Bridgham J, Broderius M, Eide D (1997) Characterization of the FET4 protein of yeast. Evidence for a direct role in the transport of iron. J Biol Chem 272:11770-11777

    PubMed  CAS  Google Scholar 

  • 30. Dix DR, Bridgham JT, Broderius MA, Byersdorfer CA, Eide DJ (1994) The FET4 gene en-codes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae. J Biol Chem 269:26092-26099

    PubMed  CAS  Google Scholar 

  • 31. Dutkiewicz R, Schilke B, Cheng S, Knieszner H, Craig EA, Marszalek J (2004) Sequence-specific interaction between mitochondrial Fe-S scaffold protein Isu and Hsp70 Ssq1 is essential for their in vivo function. J Biol Chem 279:29167-29174

    PubMed  CAS  Google Scholar 

  • 32. Eck R, Hundt S, Härtl A, Roemer E, Künkel W (1999) A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption. Microbiol 145:2415-2422

    CAS  Google Scholar 

  • 33. Eisendle M, Oberegger H, Buttinger R, Illmer P, Haas H (2004) Biosynthesis and uptake of siderophores is controlled by the PacC-mediated ambient-pH regulatory system in As-pergillus nidulans. Eukaryot Cell 3:561-563

    PubMed  CAS  PubMed Central  Google Scholar 

  • 34. Epsztejn S, Kakhlon O, Glickstein H, Breuer W, Cabantchik I (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 248:31-40

    PubMed  CAS  Google Scholar 

  • 35. Fagerstrom-Billai F, Wright AP (2005) Functional comparison of the tup11 and tup12 tran-scriptional corepressors in fission yeast. Mol Cell Biol 25:716-727

    PubMed  PubMed Central  Google Scholar 

  • 36. Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W (1998) Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Sci-ence 282:2215-2220

    Google Scholar 

  • 37. Foster LA (2002) Utilization and cell-surface binding of hemin by Histoplasma capsula-tum. Can J Microbiol 48:437-442

    PubMed  CAS  Google Scholar 

  • 38. Foury F, Roganti T (2002) Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain. J Biol Chem 277:24475-24483

    PubMed  CAS  Google Scholar 

  • 39. Foury F, Talibi D (2001) Mitochondrial control of iron homeostasis. A genome wide analy-sis of gene expression in a yeast frataxin-deficient strain. J Biol Chem 276:7762-7768

    PubMed  CAS  Google Scholar 

  • 40. Fragiadakis GS, Tzamarias D, Alexandraki D (2004) Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2 transcriptional activation. EMBO J 23:333-342

    PubMed  CAS  PubMed Central  Google Scholar 

  • 41. Frazzon J, Fick JR, Dean DR (2002) Biosynthesis of iron-sulphur clusters is a complex and highly conserved process. Biochem Soc Trans 30:680-685

    PubMed  CAS  Google Scholar 

  • 42. Gagiano M, Bauer FF, Pretorius IS (2002) The sensing of nutritional status and the rela-tionship to filamentous growth in Saccharomyces cerevisiae. FEMS Yeast Res 2:433-470

    PubMed  CAS  Google Scholar 

  • 43. Gaxiola RA, Yuan DS, Klausner RD, Fink GR (1998) The yeast CLC chloride channel functions in cation homeostasis. Proc Natl Acad Sci USA 95:4046-4050

    PubMed  CAS  PubMed Central  Google Scholar 

  • 44. Ge J, Perlstein DL, Nguyen HH, Bar G, Griffin RG, Stubbe J (2001) Why multiple small subunits (Y2 and Y4) for yeast ribonucleotide reductase? Toward understanding the role of Y4. Proc Natl Acad Sci USA 98:10067-10072

    PubMed  CAS  PubMed Central  Google Scholar 

  • 45. Georgatsou E, Alexandraki D (1994) Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae. Mol Cell Biol 14:3065-3073

    PubMed  CAS  PubMed Central  Google Scholar 

  • 46. Gerber J, Muhlenhoff U, Lill R (2003) An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep 4:906-911

    PubMed  CAS  PubMed Central  Google Scholar 

  • 47. Gerber J, Neumann K, Prohl C, Muhlenhoff U, Lill R (2004) The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S pro-teins. Mol Cell Biol 24:4848-4857

    PubMed  CAS  PubMed Central  Google Scholar 

  • 48. Greene JR, Brown NH, DiDomenico BJ, Kaplan J, Eide DJ (1993) The GEF1 gene of Sac-charomyces cerevisiae encodes an integral membrane protein; mutations in which have effects on respiration and iron-limited growth. Mol Gen Genet 241:542-553

    PubMed  CAS  Google Scholar 

  • 49. Haas H (2003) Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl Microbiol Biotechnol 62:316-330

    PubMed  CAS  Google Scholar 

  • 50. Haas H, Schoeser M, Lesuisse E, Ernst JF, Parson W, Abt B, Winkelmann G, Oberegger H (2003) Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C. Biochem J 371:505-513

    PubMed  CAS  PubMed Central  Google Scholar 

  • 51. Haas H, Zadra I, Stoeffler G, Angermayr K (1999) The Aspergillus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake. J Biol Chem 274:4613-4619

    PubMed  CAS  Google Scholar 

  • 52. Halliwell B, Gutteridge JMC (1992) Biologically relevant metal ion-dependent hydroxyl radical generation - an update. Febs Letters 307:108-112

    PubMed  CAS  Google Scholar 

  • 53. Harrison KA, Marzluf GA (2002) Characterization of DNA binding and the cysteine rich region of SRE, a GATA factor in Neurospora crassa involved in siderophore synthe-sis. Biochemistry 41:15288-15295

    PubMed  CAS  Google Scholar 

  • 54. Hassett R, Kosman DJ (1995) Evidence for Cu(II) reduction as a component of copper up-take by Saccharomyces cerevisiae. J Biol Chem 270:128-134

    PubMed  CAS  Google Scholar 

  • 55. Hassett RF, Romeo AM, Kosman DK (1998a) Regulation of high affinity iron uptake in the yeast, Saccharomyces cerevisiae. Role of dioxygen and Fe(II). J Biol Chem 273:7628-7636

    PubMed  CAS  Google Scholar 

  • 56. Hassett RF, Yuan DS, Kosman DJ (1998b) Spectral and kinetic properties of the Fet3 protein from Saccharomyces cerevisiae, a multinuclear copper ferroxidase enzyme. J Biol Chem 273:23274-23282

    PubMed  CAS  Google Scholar 

  • 57. He Y, Alam SL, Proteasa SV, Zhang Y, Lesuisse E, Dancis A, Stemmler TL (2004) Yeast frataxin solution structure, iron binding, and ferrochelatase interaction. Biochemistry 43:16254-16262

    PubMed  CAS  PubMed Central  Google Scholar 

  • 58. Heymann P, Ernst JF, Winkelmann G (1999) Identification of a fungal triacetylfusarinine C siderophore transport gene (TAF1) in Saccharomyces cerevisiae as a member of the major facilitator superfamily. Biometals 12:301-306

    PubMed  CAS  Google Scholar 

  • 59. Heymann P, Ernst JF, Winkelmann G (2000a) A gene of the major facilitator superfamily encodes a transporter for enterobactin (Enb1p) in Saccharomyces cerevisiae. Bio-metals 13:65-72

    Google Scholar 

  • 60. Heymann P, Ernst JF, Winkelmann G (2000b) Identification and substrate specificity of a ferrichrome-type siderophore transporter (Arn1p) in Saccharomyces cerevisiae. FEMS Microbiol Lett 186:221-227

    PubMed  CAS  Google Scholar 

  • 61. Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G, Ernst JF (2002) The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of fer-richrome-type siderophores and is required for epithelial invasion. Infect Immun 70:5246-5255

    PubMed  CAS  PubMed Central  Google Scholar 

  • 62. Howard DH (2004) Iron gathering by zoopathogenic fungi. FEMS Immunol Med Microbiol 40:95-100

    PubMed  CAS  Google Scholar 

  • 63. Hu CJ, Bai C, Zheng XD, Wang YM, Wang Y (2002) Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans. J Biol Chem 277:30598-30605

    PubMed  CAS  Google Scholar 

  • 64. Huang M, Elledge SJ (1997) Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae. Mol Cell Biol 17:6105-6113

    PubMed  CAS  PubMed Central  Google Scholar 

  • 65. Huffman DL, O'Halloran TV (2001) Function, structure, and mechanism of intracellular copper trafficking proteins. Annu Rev Biochem 70:677-701

    PubMed  CAS  Google Scholar 

  • 66. Huschka H, Naegeli HU, Leuenberger-Ryf H, Keller-Schierlein W, Winkelmann G (1985) Evidence for a common siderophore transport system but different siderophore recep-tors in Neurospora crassa. J Bacteriol 162:715-721

    PubMed  CAS  PubMed Central  Google Scholar 

  • 67. Kaplan J (2002) Mechanisms of cellular iron acquisition: another iron in the fire. Cell 111:603-606

    PubMed  CAS  Google Scholar 

  • 68. Kim Y, Yun CW, Philpott CC (2002) Ferrichrome induces endosome to plasma membrane cycling of the ferrichrome transporter, Arn1p, in Saccharomyces cerevisiae. EMBO J 21:3632-3642

    PubMed  CAS  PubMed Central  Google Scholar 

  • 69. Kispal G, Csere P, Guiard B, Lill R (1997) The ABC transporter Atm1p is required for mi-tochondrial iron homeostasis. FEBS Lett 418:346-350

    PubMed  CAS  Google Scholar 

  • 70. Kispal G, Csere P, Prohl C, Lill R (1999) The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. Embo J 18:3981-3989

    PubMed  CAS  PubMed Central  Google Scholar 

  • 71. Knight SA, Lesuisse E, Stearman R, Klausner RD, Dancis A (2002) Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. Microbiol 148:29-40

    CAS  Google Scholar 

  • 72. Knight SA, Sepuri NB, Pain D, Dancis A (1998) Mt-Hsp70 homolog, Ssc2p, required for maturation of yeast frataxin and mitochondrial iron homeostasis. J Biol Chem 273:18389-18393

    PubMed  CAS  Google Scholar 

  • 73. Kosman DJ (2003) Molecular mechanisms of iron uptake in fungi. Mol Microbiol 47:1185-1197

    PubMed  CAS  Google Scholar 

  • 74. La Fontaine S, Quinn JM, Nakamoto SS, Page MD, Gohre V, Moseley JL, Kropat J, Mer-chant S (2002) Copper-dependent iron assimilation pathway in the model photosyn-thetic eukaryote Chlamydomonas reinhardtii. Eukaryot Cell 1:736-757

    Google Scholar 

  • 75. Labbe S, Pena MM, Fernandes AR, Thiele DJ (1999) A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe. J Biol Chem 274:36252-36260

    PubMed  CAS  Google Scholar 

  • 76. Labbe-Bois R (1990) The ferrochelatase from Saccharomyces cerevisiae. Sequence, disrup-tion, and expression of its structural gene HEM15. J Biol Chem 265:7278-7283

    PubMed  CAS  Google Scholar 

  • 77. Lan CY, Rodarte G, Murillo LA, Jones T, Davis RW, Dungan J, Newport G, Agabian N (2004) Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol 53:1451-1469

    PubMed  CAS  Google Scholar 

  • 78. Lange H, Kispal G, Lill R (1999) Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J Biol Chem 274:18989-18996

    PubMed  CAS  Google Scholar 

  • 79. Lange H, Lisowsky T, Gerber J, Muhlenhoff U, Kispal G, Lill R (2001) An essential func-tion of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins. EMBO Rep 2:715-720

    PubMed  CAS  PubMed Central  Google Scholar 

  • 80. Lange H, Muhlenhoff U, Denzel M, Kispal G, Lill R (2004) The heme synthesis defect of mutants impaired in mitochondrial iron-sulfur protein biogenesis is caused by reversi-ble inhibition of ferrochelatase. J Biol Chem 279:29101-29108

    PubMed  CAS  Google Scholar 

  • 81. Lee J, Hofhaus G, Lisowsky T (2000) Erv1p from Saccharomyces cerevisiae is a FAD-linked sulfhydryl oxidase. FEBS Lett 477:62-66

    PubMed  CAS  Google Scholar 

  • 82. Lesuisse E, Blaiseau P-L, Dancis A, Camadro J-M (2001) Siderophore uptake and use by the yeast Saccharomyces cerevisiae. Microbiol 147:289-298

    CAS  Google Scholar 

  • 83. Lesuisse E, Knight SA, Camadro JM, Dancis A (2002) Siderophore uptake by Candida al-bicans: effect of serum treatment and comparison with Saccharomyces cerevisiae. Yeast 19:329-340

    PubMed  CAS  Google Scholar 

  • 84. Lesuisse E, Lyver ER, Knight SA, Dancis A (2004) Role of YHM1, encoding a mitochon-drial carrier protein, in iron distribution of yeast. Biochem J 378:599-607

    PubMed  CAS  PubMed Central  Google Scholar 

  • 85. Lesuisse E, Santos R, Matzanke BF, Knight SA, Camadro JM, Dancis A (2003) Iron use for haeme synthesis is under control of the yeast frataxin homologue (Yfh1). Hum Mol Genet 12:879-889

    PubMed  CAS  Google Scholar 

  • 86. Lesuisse E, Simon-Casteras M, Labbe P (1998) Siderophore-mediated iron uptake in Sac-charomyces cerevisiae: the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily. Microbiol 144:3455-3462

    CAS  Google Scholar 

  • 87. Li L, Chen OS, McVey Ward D, Kaplan J (2001) CCC1 is a transporter that mediates vacuolar iron storage in yeast. J Biol Chem 276:29515-29519

    PubMed  CAS  Google Scholar 

  • 88. Li L, Kaplan J (1997) Characterization of two homologous yeast genes that encode mito-chondrial iron transporters. J Biol Chem 272:28485-28493

    PubMed  CAS  Google Scholar 

  • 89. Li L, Kaplan J (2004) A mitochondrial-vacuolar signaling pathway in yeast that affects iron and copper metabolism. J Biol Chem 279:33653-33661

    PubMed  CAS  Google Scholar 

  • 90. Lill R, Kispal G (2001) Mitochondrial ABC transporters. Res Microbiol 152:331-340

    PubMed  CAS  Google Scholar 

  • 91. Lowry JA, Atchley WR (2000) Molecular evolution of the GATA family of transcription factors: conservation within the DNA-binding domain. J Mol Evol 50:103-115

    PubMed  CAS  Google Scholar 

  • 92. Luk E, Jensen LT, Culotta VC (2003) The many highways for intracellular trafficking of metals. J Biol Inorg Chem 8:803-809

    PubMed  CAS  Google Scholar 

  • 93. Martins LJ, Jensen LT, Simon JR, Keller GL, Winge DR (1998) Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae. J Biol Chem 273:23716-23721

    PubMed  CAS  Google Scholar 

  • 94. Marvin ME, Mason RP, Cashmore AM (2004) The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactiva-tor encoded by CaMAC1. Microbiol 150:2197-2208

    CAS  Google Scholar 

  • 95. Matzanke BF, Anemuller S, Schunemann V, Trautwein AX, Hantke K (2004) FhuF, part of a siderophore-reductase system. Biochemistry 43:1386-1392

    PubMed  CAS  Google Scholar 

  • 96. Medlock AE, Dailey HA (2000) Examination of the activity of carboxyl-terminal chimeric constructs of human and yeast ferrochelatases. Biochemistry 39:7461-7467

    PubMed  CAS  Google Scholar 

  • 97. Muhlenhoff U, Balk J, Richhardt N, Kaiser JT, Sipos K, Kispal G, Lill R (2004) Functional characterization of the eukaryotic cysteine desulfurase Nfs1p from Saccharomyces cerevisiae. J Biol Chem 279:36906-36915

    PubMed  Google Scholar 

  • 98. Muhlenhoff U, Gerber J, Richhardt N, Lill R (2003a) Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J 22:4815-4825

    PubMed  PubMed Central  Google Scholar 

  • 99. Muhlenhoff U, Richhardt N, Gerber J, Lill R (2002) Characterization of iron-sulfur protein assembly in isolated mitochondria. A requirement for ATP, NADH, and reduced iron. J Biol Chem 277:29810-29816

    PubMed  CAS  Google Scholar 

  • 100. Muhlenhoff U, Stadler JA, Richhardt N, Seubert A, Eickhorst T, Schweyen RJ, Lill R, Wiesenberger G (2003b) A specific role of the yeast mitochondrial carriers MRS3/4p in mitochondrial iron acquisition under iron-limiting conditions. J Biol Chem 278:40612-40620

    PubMed  Google Scholar 

  • 101. Napier I, Ponka P, Richardson DR (2004) Iron trafficking in the mitochondrion: novel pathways revealed by disease. Blood

    Google Scholar 

  • 102. Neilands JB (1995) Siderophores: structure and function of microbial iron transport com-pounds. J Biol Chem 270:26723-26726

    PubMed  CAS  Google Scholar 

  • 103. Nelson N (1999) Metal ion transporters and homeostasis. EMBO J 18:4361-4371

    PubMed  CAS  PubMed Central  Google Scholar 

  • 104. Nguyen HH, Ge J, Perlstein DL, Stubbe J (1999) Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from yeast: Y4 plays a key role in diiron cluster assem-bly. Proc Natl Acad Sci USA 96:12339-12344

    PubMed  CAS  PubMed Central  Google Scholar 

  • 105. Oberegger H, Schoeser M, Zadra I, Abt B, Haas H (2001) SREA is involved in regulation of siderophore biosynthesis, utilization and uptake in Aspergillus nidulans. Mol Mi-crobiol 41:1077-1089

    Google Scholar 

  • 106. Oberegger H, Schoeser M, Zadra I, Schrettl M, Parson W, Haas H (2002a) Regulation of freA, acoA, lysF, and cycA expression by iron availability in Aspergillus nidulans. Appl Environ Microbiol 68:5769-5772

    PubMed  CAS  PubMed Central  Google Scholar 

  • 107. Oberegger H, Zadra I, Schoeser M, Abt B, Parson W, Haas H (2002b) Identification of members of the Aspergillus nidulans SREA regulon: genes involved in siderophore biosynthesis and utilization. Biochem Soc Trans 30:781-783

    PubMed  CAS  Google Scholar 

  • 108. Pelletier B, Beaudoin J, Mukai Y, Labbe S (2002) Fep1, an iron sensor regulating iron transporter gene expression in Schizosaccharomyces pombe. J Biol Chem 277:22950-22958

    PubMed  CAS  Google Scholar 

  • 109. Pelletier B, Beaudoin J, Philpott CC, Labbe S (2003) Fep1 represses expression of the fis-sion yeast Schizosaccharomyces pombe siderophore-iron transport system. Nucleic Ac-ids Res 31:4332-4344

    Google Scholar 

  • 110. Philpott CC, Protchenko O, Kim YW, Boretsky Y, Shakoury-Elizeh M (2002) The re-sponse to iron deprivation in Saccharomyces cerevisiae: expression of siderophore-based systems of iron uptake. Biochem Soc Trans 30:698-702

    PubMed  CAS  Google Scholar 

  • 111. Portnoy ME, Liu XF, Culotta VC (2000) Saccharomyces cerevisiae expresses three func-tionally distinct homologues of the nramp family of metal transporters. Mol Cell Biol 20:7893-7902

    PubMed  CAS  PubMed Central  Google Scholar 

  • 112. Protchenko O, Ferea T, Rashford J, Tiedeman J, Brown PO, Botstein D, Philpott CC (2001) Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cere-visiae. J Biol Chem 276:49244-49250

    PubMed  CAS  Google Scholar 

  • 113. Protchenko O, Philpott CC (2003) Regulation of intracellular heme levels by HMX1, a homologue of heme oxygenase, in Saccharomyces cerevisiae. J Biol Chem 278:36582-36587

    PubMed  CAS  Google Scholar 

  • 114. Puig S, Askeland E, Thiele DJ (2005) Coordinated remodeling of cellular metabolism dur-ing iron deficiency through targeted mRNA degradation. Cell 120:99-110

    PubMed  CAS  Google Scholar 

  • 115. Puig S, Lau M, Thiele DJ (2004) Cti6 is an Rpd3-Sin3 histone deacetylase-associated pro-tein required for growth under iron-limiting conditions in Saccharomyces cerevisiae. J Biol Chem 279:30298-30306

    PubMed  CAS  Google Scholar 

  • 116. Radisky DC, B. SW, Emr SD, Kaplan J (1997) Characterization of VPS41, a gene required for vacuolar trafficking and high-affinity iron transport in yeast. Proc Natl Acad Sci USA 94:5662-5666

    PubMed  CAS  PubMed Central  Google Scholar 

  • 117. Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O'Halloran TV (1999) Undetectable intracel-lular free copper: the requirement of a copper chaperone for superoxide dismutase. Science 284:805-808

    PubMed  CAS  Google Scholar 

  • 118. Raguzzi F, Lesuisee E, Crichton RR (1988) Iron storage in Saccharomyces cerevisiae. FEBS Lett 231:253-258

    PubMed  CAS  Google Scholar 

  • 119. Ramanan N, Wang Y (2000) A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062-1064

    PubMed  CAS  Google Scholar 

  • 120. Ramazzotti A, Vanmansart V, Foury F (2004) Mitochondrial functional interactions be-tween frataxin and Isu1p, the iron-sulfur cluster scaffold protein, in Saccharomyces cerevisiae. FEBS Lett 557:215-220

    PubMed  CAS  Google Scholar 

  • 121. Roman Dragos G, Dancis A, Anderson GJ, Klausner R, D. (1993) The fission yeast ferric reductase gene frp1 positive is required for ferric iron uptake and encodes a protein that is homologous to the gp91-phox subunit of the human NADPH phagocyte oxi-doreductase. Mol Cell Biol 13:4342-4350

    PubMed  CAS  PubMed Central  Google Scholar 

  • 122. Rouault TA (2004) Microbiology. Pathogenic bacteria prefer heme. Science 305:1577-1578

    PubMed  CAS  Google Scholar 

  • 123. Rutherford JC, Bird AJ (2004) Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot Cell 3:1-13

    PubMed  CAS  PubMed Central  Google Scholar 

  • 124. Rutherford JC, Jaron S, Ray E, Brown PO, Winge DR (2001) A second iron-regulatory sys-tem in yeast independent of Aft1p. Proc Natl Acad Sci USA 98:14322-14327

    PubMed  CAS  PubMed Central  Google Scholar 

  • 125. Rutherford JC, Jaron S, Winge DR (2003) Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements. J Biol Chem 278:27636-27643

    PubMed  CAS  Google Scholar 

  • 126. Rutherford JC, Ojeda L, Balk J, Muhlenhoff U, Lill R, Winge DR (2005) Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial, but not cytosolic iron-sulfur protein biogenesis. J Biol Chem published on-line

    Google Scholar 

  • 127. Santos R, Buisson N, Knight S, Dancis A, Camadro JM, Lesuisse E (2003) Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxy-genase. Microbiol 149:579-588

    CAS  Google Scholar 

  • 128. Sauer M, Hantke K, Braun V (1990) Sequence of the fhuE outer-membrane receptor gene of Escherichia coli K12 and properties of mutants. Mol Microbiol 4:427-437

    PubMed  CAS  Google Scholar 

  • 129. Schroder I, Johnson E, de Vries S (2003) Microbial ferric iron reductases. FEMS Microbiol Rev 27:427-447

    PubMed  CAS  Google Scholar 

  • 130. Schwappach B, Stobrawa S, Hechenberger M, Steinmeyer K, Jentsch TJ (1998) Golgi lo-calization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1p. J Biol Chem 273:15110-15118

    PubMed  CAS  Google Scholar 

  • 131. Severance S, Chakraborty S, Kosman DJ (2004) The Ftr1p iron permease in the yeast plasma membrane: orientation, topology and structure-function relationships. Biochem J 380:487-496

    PubMed  CAS  PubMed Central  Google Scholar 

  • 132. Shakoury-Elizeh M, Tiedeman J, Rashford J, Ferea T, Demeter J, Garcia E, Rolfes R, Brown PO, Botstein D, Philpott CC (2004) Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae. Mol Biol Cell 15:1233-1243

    PubMed  CAS  PubMed Central  Google Scholar 

  • 133. Smith RL, Johnson AD (2000) Turning genes off by Ssn6-Tup1: a conserved system of transcriptional repression in eukaryotes. Trends Biochem Sci 25:325-330

    PubMed  CAS  Google Scholar 

  • 134. Srinivasan C, Liba A, Imlay JA, Valentine JS, Gralla EB (2000) Yeast lacking superoxide dismutase(s) show elevated levels of ”free iron” as measured by whole cell electron paramagnetic resonance. J Biol Chem 275:29187-29192

    PubMed  CAS  Google Scholar 

  • 135. Stearman R, Yuan DS, Yamaguchi-Iwai Y, Klausner RD, Dancis A (1996) A permease-oxidase complex involved in high-affinity iron uptake in yeast. Science 271:1552-1557

    PubMed  CAS  Google Scholar 

  • 136. Stubbe J, Riggs-Gelasco P (1998) Harnessing free radicals: formation and function of the tyrosyl radical in ribonucleotide reductase. Trends Biochem Sci 23:438-443

    PubMed  CAS  Google Scholar 

  • 137. Tan PK, Howard JP, Payne GS (1996) The sequence NPFXD defines a new class of endo-cytosis signal in Saccharomyces cerevisiae. J Cell Biol 135:1789-1800

    PubMed  CAS  Google Scholar 

  • 138. Thomas F, Serratrice G, Beguin C, Aman ES, Pierre JL, Fontecave M, Laulhere JP (1999) Calcein as a fluorescent probe for ferric iron. Application to iron nutrition in plant cells. J Biol Chem 274:13375-13383

    PubMed  CAS  Google Scholar 

  • 139. Timmerman MM, Woods JP (1999) Ferric reduction is a potential iron acquisition mecha-nism for Histoplasma capsulatum. Infect Immun 67:6403-6408

    PubMed  CAS  PubMed Central  Google Scholar 

  • 140. Timmerman MM, Woods JP (2001) Potential role for extracellular glutathione-dependent ferric reductase in utilization of environmental and host ferric compounds by Histo-plasma capsulatum. Infect Immun 69:7671-7678

    PubMed  CAS  PubMed Central  Google Scholar 

  • 141. Ueta R, Fukunaka A, Yamaguchi-Iwai Y (2003) Pse1p mediates the nuclear import of the iron-responsive transcription factor Aft1p in Saccharomyces cerevisiae. J Biol Chem 278:50120-50127

    PubMed  CAS  Google Scholar 

  • 142. Urbanowski JL, Piper RC (1999) The iron transporter Fth1p forms a complex with the Fet5 iron oxidase and resides on the vacuolar membrane. J Biol Chem 274:38061-38070

    PubMed  CAS  Google Scholar 

  • 143. Van Ho A, Ward DM, Kaplan J (2002) Transition metal transport in yeast. Annu Rev Mi-crobiol 56:237-261

    Google Scholar 

  • 144. Wang TP, Quintanar L, Severance S, Solomon EI, Kosman DJ (2003) Targeted suppression of the ferroxidase and iron trafficking activities of the multicopper oxidase Fet3p from Saccharomyces cerevisiae. J Biol Inorg Chem 8:611-620

    PubMed  CAS  Google Scholar 

  • 145. Weissman Z, Kornitzer D (2004) A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53:1209-1220

    PubMed  CAS  Google Scholar 

  • 146. Winkelmann G (2002) Microbial siderophore-mediated transport. Biochem Soc Trans 30:691-696

    PubMed  CAS  Google Scholar 

  • 147. Voegtli WC, Ge J, Perlstein DL, Stubbe J, Rosenzweig AC (2001) Structure of the yeast ri-bonucleotide reductase Y2Y4 heterodimer. Proc Natl Acad Sci USA 98:10073-10078

    PubMed  CAS  PubMed Central  Google Scholar 

  • 148. Voisard C, Wang J, McEvoy JL, Xu P, Leong SA (1993) urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Biol 13:7091-7100

    PubMed  CAS  PubMed Central  Google Scholar 

  • 149. Voisine C, Cheng YC, Ohlson M, Schilke B, Hoff K, Beinert H, Marszalek J, Craig EA (2001) Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe/S clusters in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 98:1483-1488

    PubMed  CAS  PubMed Central  Google Scholar 

  • 150. Vozza A, Blanco E, Palmieri L, Palmieri F (2004) Identification of the mitochondrial GTP/GDP transporter in Saccharomyces cerevisiae. J Biol Chem 279:20850-20857

    PubMed  CAS  Google Scholar 

  • 151. Yamaguchi-Iwai Y, Dancis A, Klausner RD (1995) AFT1: A mediator of iron-regulated transcriptional control in Saccharomyces cerevisiae. EMBO J 14:1231-1239

    PubMed  CAS  PubMed Central  Google Scholar 

  • 152. Yamaguchi-Iwai Y, Serpe M, Haile D, Yang W, Kosman DJ, Klausner RD, Dancis A (1997) Homeostatic regulation of copper uptake in yeast via direct binding of MAC1 protein to upstream regulatory sequences of FRE1 and CTR1. J Biol Chem 272:17711-17718

    PubMed  CAS  Google Scholar 

  • 153. Yamaguchi-Iwai Y, Stearman R, Dancis A, Klausner RD (1996) Iron-regulated DNA bind-ing by the AFT1 protein controls the iron regulon in yeast. EMBO J 15:3377-3384

    PubMed  CAS  PubMed Central  Google Scholar 

  • 154. Yamaguchi-Iwai Y, Ueta R, Fukunaka A, Sasaki R (2002) Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae. J Biol Chem 277:18914-18918

    PubMed  CAS  Google Scholar 

  • 155. Yoon T, Cowan JA (2003) Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins. J Am Chem Soc 125:6078-6084

    PubMed  CAS  Google Scholar 

  • 156. Yoon T, Cowan JA (2004) Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis. J Biol Chem 279:25943-25946

    PubMed  CAS  Google Scholar 

  • 157. Yun C-W, Bauler M, Moore RE, Klebba PE, Philpott CC (2001) The role of the FRE fam-ily of plasma membrane reductases in the uptake of siderophore-iron in Saccharomy-ces cerevisiae. J Biol Chem 276:10218-10223

    PubMed  CAS  Google Scholar 

  • 158. Yun C-W, Tiedeman J, Moore RE, Philpott CC (2000) Siderophore-iron uptake in Sac-charomyces cerevisiae. Identification of ferrichrome and fusarinine transporters. J Biol Chem 275:16354-16359

    PubMed  CAS  Google Scholar 

  • 159. Zhou L, Marzluf GA (1999) Functional analysis of the two zinc fingers of SRE, a GATA-type factor that negatively regulates siderophore synthesis in Neurospora crassa. Bio-chemistry 38:4335-4341

    Google Scholar 

  • 160. Zhou L-W, Haas H, Marzluf GA (1998) Isolation and characterization of a new gene, sre, which encodes a GATA-type regulatory protein that controls iron transport in Neuro-spora crassa. Mol Gen Gen 259:532-540

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Markus J. Tamas Enrico Martinoia

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kwok, E., Kosman, D. (2005). Iron in yeast: Mechanisms involved in homeostasis. In: Tamas, M.J., Martinoia, E. (eds) Molecular Biology of Metal Homeostasis and Detoxification. Topics in Current Genetics, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_92

Download citation

Publish with us

Policies and ethics