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Genome-wide screening of yeast metal homeostasis genes involved in mitochondrial functions

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Abstract

Metal ions are essential for mitochondria to execute their roles. Yeast mutants that are sensitive to metals (either excess or deficiency) on non-fermentable media but not on fermentable media may carry mutations in genes that participate in metal homeostasis involving mitochondrial functions. A collection of approximately 4,800 haploid yeast deletion mutants was screened for metal ion homeostasis genes linked to mitochondrial respiration. In addition to several well-characterized metal homeostasis genes, 45 new mutants, impaired in various molecular functions, were identified on non-fermentable media that were sensitive to adscititious metals or metal deficiency. While 35 of these mutants displayed metal-sensitivity only on non-fermentable media, the remaining 10 also exhibited metal sensitivity on fermentable media, suggesting metal-sensitivity of the latter is not due to mitochondrial dysfunction. Inductively coupled plasma optical emission spectrometry (ICP-OES) was conducted for 12 mutants that were sensitive to metal excess to analyze their metal contents. Among these 12 mutants 7 were sensitive to metal excess on non-fermentable but not on fermentable media. All the seven respiration-dependent mutants displayed abnormal levels of metal ions inside mitochondria, indicative of disrupted mitochondrial metal homeostasis. This study therefore effectively identified multiple new genes involved in metal homeostasis pathways possibly pertinent to mitochondrial functions, and should be helpful for future studies to further understand their molecular roles.

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References

  • Askwith C et al (1994) The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell 76:403–410

    Article  PubMed  CAS  Google Scholar 

  • Babcock M et al (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276:1709–1712

    Article  PubMed  CAS  Google Scholar 

  • Dancis A, Klausner RD, Hinnebusch AG, Barriocanal JG (1990) Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae. Mol Cell Biol 10:2294–2301

    PubMed  CAS  Google Scholar 

  • Dancis A et al (1994) Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport. Cell 76:393–402

    Article  PubMed  CAS  Google Scholar 

  • Daum G, Bohni PC, Schatz G (1982) Import of proteins into mitochondria. Cytochrome b2 and cytochrome c peroxidase are located in the intermembrane space of yeast mitochondria. J Biol Chem 257:13028–13033

    PubMed  CAS  Google Scholar 

  • Dean JA (1999) Lange’s handbook of chemistry, 15th edn. McGraw-Hill, Inc., New York

    Google Scholar 

  • Dimmer KS et al (2002) Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell 13:847–853

    Article  PubMed  CAS  Google Scholar 

  • Durr G et al (1998) The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2+ and Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell 9:1149–1162

    PubMed  CAS  Google Scholar 

  • Eide DJ et al (2005) Characterization of the yeast ionome: a genome-wide analysis of nutrient mineral and trace element homeostasis in Saccharomyces cerevisiae. Genome Biol 6:R77

    Article  PubMed  Google Scholar 

  • 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  Google Scholar 

  • Georgatsou E, Mavrogiannis LA, Fragiadakis GS, Alexandraki D (1997) The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator. J Biol Chem 272:13786–13792

    Article  PubMed  CAS  Google Scholar 

  • Glerum DM, Shtanko A, Tzagoloff A (1996a) Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. J Biol Chem 271:14504–14509

    Article  CAS  Google Scholar 

  • Glerum DM, Shtanko A, Tzagoloff A (1996b) SCO1 and SCO2 act as high copy suppressors of a mitochondrial copper recruitment defect in Saccharomyces cerevisiae. J Biol Chem 271:20531–20535

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hwang CS et al (1999) Copper- and zinc-containing superoxide dismutase and its gene from Candida albicans. Biochim Biophys Acta 1427:245–255

    PubMed  CAS  Google Scholar 

  • Labbe S, Zhu Z, Thiele DJ (1997) Copper-specific transcriptional repression of yeast genes encoding critical components in the copper transport pathway. J Biol Chem 272:15951–15958

    Article  PubMed  CAS  Google Scholar 

  • Lapinskas PJ, Cunningham KW, Liu XF, Fink GR, Culotta VC (1995) Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase. Mol Cell Biol 15:1382–1388

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lin SJ, Culotta VC (1995) The ATX1 gene of Saccharomyces cerevisiae encodes a small metal homeostasis factor that protects cells against reactive oxygen toxicity. Proc Natl Acad Sci USA 92:3784–3788

    Article  PubMed  CAS  Google Scholar 

  • Lin SJ, Pufahl RA, Dancis A, O’Halloran TV, Culotta VC (1997) A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport. J Biol Chem 272:9215–9220

    Article  PubMed  CAS  Google Scholar 

  • Luk E, Carroll M, Baker M, Culotta VC (2003) Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family. Proc Natl Acad Sci USA 100:10353–10357

    Article  PubMed  CAS  Google Scholar 

  • MacDiarmid CW, Gaither LA, Eide D (2000) Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. EMBO J 19:2845–2855

    Article  PubMed  CAS  Google Scholar 

  • Miyabe S, Izawa S, Inoue Y (2000) Expression of ZRC1 coding for suppressor of zinc toxicity is induced by zinc-starvation stress in Zap1–dependent fashion in Saccharomyces cerevisiae. Biochem Biophys Res Commun 276:879–884

    Article  PubMed  CAS  Google Scholar 

  • Miyabe S, Izawa S, Inoue Y (2001) The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae. Biochem Biophys Res Commun 282:79–83

    Article  PubMed  CAS  Google Scholar 

  • Muhlenhoff U et al (2003) A specific role of the yeast mitochondrial carriers MRS3/4p in mitochondrial iron acquisition under iron-limiting conditions. J Biol Chem 278:40612–40620

    Article  PubMed  Google Scholar 

  • Ramsay LM, Gadd GM (1997) Mutants of Saccharomyces cerevisiae defective in vacuolar function confirm a role for the vacuole in toxic metal ion detoxification. FEMS Microbiol Lett 152:293–298

    Article  PubMed  CAS  Google Scholar 

  • Supek F, Supekova L, Nelson H, Nelson N (1996) A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc Natl Acad Sci USA 93:5105–5110

    Article  PubMed  CAS  Google Scholar 

  • Wilson RB, Roof DM (1997) Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat Genet 16:352–357

    Article  PubMed  CAS  Google Scholar 

  • 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  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Yuan DS, Stearman R, Dancis A, Dunn T, Beeler T, Klausner RD (1995) The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake. Proc Natl Acad Sci USA 92:2632–2636

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Eide D (1996) The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation. Proc Natl Acad Sci USA 93:2454–2458

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Eide DJ (1997) Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional regulation in Saccharomyces cerevisiae. Mol Cell Biol 17:5044–5052

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by National Science Foundation of China (#30470973 and #30528004).

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Authors and Affiliations

  1. State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, 100084, China

    Juexuan Wang, Xiaoxi Wang, Ying Fang & Bing Zhou

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  1. Juexuan Wang
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  2. Xiaoxi Wang
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  3. Ying Fang
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  4. Bing Zhou
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Correspondence to Bing Zhou.

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Communicated by S. Hohmann.

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Wang, J., Wang, X., Fang, Y. et al. Genome-wide screening of yeast metal homeostasis genes involved in mitochondrial functions. Mol Genet Genomics 277, 673–683 (2007). https://doi.org/10.1007/s00438-007-0217-1

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  • DOI: https://doi.org/10.1007/s00438-007-0217-1

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