Skip to main content
SpringerLink
Log in

The Role of Mortalin in Iron Homeostasis

  • Chapter
  • First Online:
Mortalin Biology: Life, Stress and Death

Abstract

The role of chaperones in prokaryotic and eukaryotic iron-sulfur cluster assembly pathways is discussed in the context of the complex sequence of events that are involved in [2Fe–2S] cluster biogenesis. Building from a background description of the functions of the component proteins and the various stages of cluster assembly and transfer to target proteins, similarities and differences in chaperone functions are presented with a particular focus on the unique characteristics of mortalin, relative to other chaperones.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • 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

Institutional subscriptions

References

  • Acebrón SP, Fernández-Sáiz V, Taneva SG, Moro F, Muga A (2008) DnaJ recruits DnaK to protein aggregates. J Biol Chem 283:1381–1390

    Article  PubMed  CAS  Google Scholar 

  • Adam AC, Bornhövd C, Prokisch H, Neupert W, Hell K (2006) The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria. EMBO J 25:174–183

    Article  PubMed  CAS  Google Scholar 

  • Agar JN, Zheng L, Cash, VL, Dean DR, Johnson MK (2000) Role of the IscU protein in iron-sulfur cluster biosynthesis: IscS-mediated assembly of a [Fe2S2] cluster in IscU. J Am Chem Soc 122:2136–2137

    Article  CAS  Google Scholar 

  • Albrecht AG, Netz DJ, Miethke M, Pierik AJ, Burghaus O, Peuckert F, Lill R, Marahiel MA (2010) SufU is an essential iron-sulfur cluster scaffold protein in Bacillus subtilis. J Bacteriol 192:1643–1651

    Article  PubMed  CAS  Google Scholar 

  • Aloria K, Schilke B, Andrew A, Craig EA (2004) Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo. EMBO Rep 5:1096–1101

    Article  PubMed  CAS  Google Scholar 

  • Alves R, Herrero E, Sorribas A (2004) Predictive reconstruction of the mitochondrial iron-sulfur cluster assembly metabolism. II. Role of glutaredoxin Grx5. Proteins 57:481–492

    Article  PubMed  CAS  Google Scholar 

  • Amutha B, Gordon DM, Gu Y, Lyver ER, Dancis A, Pain D (2008) GTP is required for iron-sulfur cluster biogenesis in mitochondria. J Biol Chem 283:1362–1371

    Article  PubMed  CAS  Google Scholar 

  • Andrew AJ, Song JY, Schilke B, Craig EA (2008) Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu. Mol Biol Cell 19:5259–5266

    Article  PubMed  CAS  Google Scholar 

  • Barras F, Loiseau L, Py B (2005) How Escherichia coli and Saccharomyces cerevisiae build Fe/S proteins. Adv Microb Physiol 50:41–101

    Article  PubMed  CAS  Google Scholar 

  • Beinert H (2000) Iron-sulfur proteins: ancient structures, still full of surprises. J Biol Inorg Chem 5:2–15

    Article  PubMed  CAS  Google Scholar 

  • Bencze KZ, Kondapalli KC, Cook JD, McMahon S, Millán-Pacheco C, Pastor N, Stemmler TL (2006) The structure and function of frataxin. Crit Rev Biochem Mol Biol 41:269–291

    Article  PubMed  CAS  Google Scholar 

  • Bencze KZ, Yoon T, Millán-Pacheco C, Bradley PB, Pastor N, Cowan JA, Stemmler TL (2007) Human frataxin: iron and ferrochelatase binding surface. Chem Commun 18:1798–1800

    Article  CAS  Google Scholar 

  • Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ER (2009) Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proc Natl Acad Sci USA 106:8471–8476

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharyya T, Karnezis AN, Murphy SP, Hoang T, Freeman BC, Phillips B, Morimoto RI (1995) Cloning and subcellular localization of human mitochondrial hsp70. J Biol Chem 270:1705–1710

    Article  PubMed  CAS  Google Scholar 

  • Biederbick A, Stehling O, Rösser R, Niggemeyer B, Nakai Y, Elsässer HP, Lill R (2006) Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation. Mol Cell Biol 26:5675–5687

    Article  PubMed  CAS  Google Scholar 

  • Blamowska M, Sichting M, Mapa K, Mokranjac D, Neupert W, Hell K (2010) ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1. J Biol Chem 285:4423–4431

    Article  PubMed  CAS  Google Scholar 

  • Bonomi F, Iametti S, Ta D, Vickery LE (2005) Multiple turnover transfer of [2Fe2S] clusters by the iron-sulfur cluster assembly scaffold proteins IscU and IscA. J Biol Chem 280:29513–29518

    Article  PubMed  CAS  Google Scholar 

  • Bonomi F, Iametti S, Morleo A, Ta D, Vickery LE (2008) Studies on the mechanism of catalysis of iron-sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry 47:12795–12801

    Article  PubMed  CAS  Google Scholar 

  • Buchberger A, Theyssen H, Schröder H, McCarty JS, Virgallita G, Milkereit P, Reinstein J, Bukau B (1995) Nucleotide-induced conformational changes in the ATPase and substrate binding domains of the DnaK chaperone provide evidence for interdomain communication. J Biol Chem 270:16903–16910

    Article  PubMed  CAS  Google Scholar 

  • Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351–366

    Article  PubMed  CAS  Google Scholar 

  • Chahal HK, Dai Y, Saini A, Ayala-Castro C, Outten FW (2009) The SufBCD Fe-S scaffold complex interacts with SufA for Fe-S cluster transfer. Biochemistry 48:10644–10653

    Article  PubMed  CAS  Google Scholar 

  • Chandramouli K, Johnson MK (2006) HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 45:11087–11095

    Article  PubMed  CAS  Google Scholar 

  • Chang HC, Tang YC, Hayer-Hartl M, Hartl FU (2007) SnapShot: molecular chaperones, part I. Cell 128:212

    Article  PubMed  Google Scholar 

  • Chang YW, Sun YJ, Wang C, Hsiao CD (2008) Crystal structures of the 70-kDa heat shock proteins in domain disjoining conformation. J Biol Chem 283:15502–15511

    Article  PubMed  CAS  Google Scholar 

  • Chen CA, Cowan JA (2006) Characterization of Saccharomyces cerevisiae Atm1p: functional studies of an ABC7 type transporter. Biochim Biophys Acta 1760:1857–1865

    Article  PubMed  CAS  Google Scholar 

  • Chen OS, Hemenway S, Kaplan J (2002) Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: evidence that Yfh1p affects Fe-S cluster synthesis. Proc Natl Acad Sci USA 99:12321–12326

    Article  PubMed  CAS  Google Scholar 

  • Chillappagari S, Seubert A, Trip H, Kuipers OP, Marahiel MA, Miethke M (2010) Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis. J Bacteriol 192:2512–2524

    Article  PubMed  CAS  Google Scholar 

  • Cook JD, Kondapalli KC, Rawat S, Childs WC, Murugesan Y, Dancis A, Stemmler TL (2010) Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly. Biochemistry 49:8756–8765

    Article  PubMed  CAS  Google Scholar 

  • Correia AR, Wang T, Craig EA, Gomes CM (2010) Iron-binding activity in yeast frataxin entails a trade off with stability in the alpha1/beta1 acidic ridge region. Biochem J 426:197–203

    Article  PubMed  CAS  Google Scholar 

  • Craig EA, Marszalek J (2002) A specialized mitochondrial molecular chaperone system: a role in formation of Fe/S centers. Cell Mol Life Sci 59:1658–1665

    Article  PubMed  CAS  Google Scholar 

  • de Mena L, Coto E, Sánchez-Ferrero E, Ribacoba R, Guisasola LM, Salvador C, Blázquez M, Alvarez V (2009) Mutational screening of the mortalin gene (HSPA9) in Parkinson’s disease. J Neural Transm 116:1289–1293

    Article  PubMed  CAS  Google Scholar 

  • Deocaris CC, Kaul SC, Wadhwa R (2006) On the brotherhood of the mitochondrial chaperones mortalin and heat shock protein 60. Cell Stress Chaperones 11:116–128

    Article  PubMed  CAS  Google Scholar 

  • Deocaris CC, Kaul SC, Wadhwa R (2008) From proliferative to neurological role of an hsp70 stress chaperone, mortalin. Biogerontology 9, 391–403

    Article  PubMed  CAS  Google Scholar 

  • Deocaris CC, Kaul SC, Wadhwa R (2009) The versatile stress protein mortalin as a chaperone therapeutic agent. Protein Pept Lett 16, 517–529

    Article  PubMed  CAS  Google Scholar 

  • Ding H, Clark RJ (2004) Characterization of iron binding in IscA, an ancient iron-sulphur cluster assembly protein. Biochem J 379:433–440

    Article  PubMed  CAS  Google Scholar 

  • Ding H, Clark RJ, Ding B (2004) IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under the limited accessible free iron conditions. J Biol Chem 279:37499–37504

    Article  PubMed  CAS  Google Scholar 

  • Dolezal P, Dancis A, Lesuisse E, Sutak R, Hrdý I, Embley TM, Tachezy J (2007) Frataxin, a conserved mitochondrial protein, in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell 6:1431–1438

    Article  PubMed  CAS  Google Scholar 

  • Dos Santos PC, Johnson DC, Ragle BE, Unciuleac MC, Dean DR (2007) Controlled expression of nif and isc iron-sulfur protein maturation components reveals target specificity and limited functional replacement between the two systems. J Bacteriol 189:2854–2862

    Article  PubMed  CAS  Google Scholar 

  • D’Silva P, Liu Q, Walter W, Craig EA (2004) Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nat Struct Mol Biol 11:1084–1091

    Article  PubMed  CAS  Google Scholar 

  • Dutkiewicz R, Schilke B, Knieszner H, Walter W, Craig EA, Marszalek J (2003) Ssq1, a mitochondrial Hsp70 involved in iron-sulfur (Fe/S) center biogenesis. Similarities to and differences from its bacterial counterpart. J Biol Chem 278:29719–29727

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Dutkiewicz R, Marszalek J, Schilke B, Craig EA, Lill R, Mühlenhoff U (2006) The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. J Biol Chem 281:7801–7808

    Article  PubMed  CAS  Google Scholar 

  • Eccleston JF, Petrovic A, Davis CT, Rangachari K, Wilson RJ (2006) The kinetic mechanism of the SufC ATPase: the cleavage step is accelerated by SufB. J Biol Chem 281:8371–8378

    Article  PubMed  CAS  Google Scholar 

  • Fantino JR, Py B, Fontecave M, Barras F (2010) A genetic analysis of the response of Escherichia coli to cobalt stress. Environ Microbiol 12:2846–2857

    PubMed  CAS  Google Scholar 

  • Farr CD, Slepenkov SV, Witt SN (1998) Visualization of a slow, ATP-induced structural transition in the bacterial molecular chaperone DnaK. J Biol Chem 273:9744–9748

    Article  PubMed  CAS  Google Scholar 

  • Fontecave M, Choudens SO, Py B, Barras F (2005) Mechanisms of iron-sulfur cluster assembly: the SUF machinery. J Biol Inorg Chem 10:713–721

    Article  PubMed  CAS  Google Scholar 

  • Fontecave M, Ollagnier-de-Choudens, S (2008) Iron-sulfur cluster biosynthesis in bacteria: mechanisms of cluster assembly and transfer. Arch Biochem Biophys 474:226–237

    Article  PubMed  CAS  Google Scholar 

  • Fosset C, Chauveau MJ, Guillon B, Canal F, Drapier JC, Bouton C (2006) RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in mitochondria and cytosol of mammalian cells. J Biol Chem 281:25398–25406

    Article  PubMed  CAS  Google Scholar 

  • Foury F, Pastore A, Trincal M (2007) Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly. EMBO Rep 8:194–199

    Article  PubMed  CAS  Google Scholar 

  • Frausto da Silva JJR, Williams RJP (2001) The biological chemistry of the elements. Oxford University Press, New York.

    Google Scholar 

  • Füzéry AK, Tonelli M, Ta DT, Cornilescu G, Vickery LE, Markley JL (2008) Solution structure of the iron-sulfur cluster cochaperone HscB and its binding surface for the iron-sulfur assembly scaffold protein IscU. Biochemistry 47:9394–9404

    Article  PubMed  CAS  Google Scholar 

  • Füzéry AK, Oh JJ, Ta DT, Vickery LE, Markley JL (2011) Three hydrophobic amino acids in Escherichia coli HscB make the greatest contribution to the stability of the HscB-IscU complex. BMC Biochem 12:3

    Google Scholar 

  • Gakh O, Adamec J, Gacy AM, Twesten RD, Owen WG, Isaya G (2002) Physical evidence that yeast frataxin is an iron storage protein. Biochemistry 41:6798–6804

    Article  PubMed  CAS  Google Scholar 

  • Gakh O, Smith DY 4th, Isaya G (2008) Assembly of the iron-binding protein frataxin in Saccharomyces cerevisiae responds to dynamic changes in mitochondrial iron influx and stress level. J Biol Chem 283:31500–31510

    Article  PubMed  CAS  Google Scholar 

  • Garland SA, Hoff K, Vickery LE, Culotta VC (1999) Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J Mol Biol 294:897–907

    Article  PubMed  CAS  Google Scholar 

  • Germot A, Philippe H, Le Guyader H (1997) Evidence for loss of mitochondria in Microsporidia from a mitochondrial-type HSP70 in Nosema locustae. Mol Biochem Parasitol 87:159–168

    Article  PubMed  CAS  Google Scholar 

  • Godman J, Balk J (2008) Genome analysis of Chlamydomonas reinhardtii reveals the existence of multiple, compartmentalized iron-sulfur protein assembly machineries of different evolutionary origins. Genetics 179:59–68

    Article  PubMed  CAS  Google Scholar 

  • Goldberg AV, Molik S, Tsaousis AD, Neumann K, Kuhnke G, Delbac F, Vivares CP, Hirt RP, Lill R, Embley TM (2008) Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature 452:624–628

    Article  PubMed  CAS  Google Scholar 

  • Gupta V, Sendra M, Naik SG, Chahal HK, Huynh BH, Outten FW, Fontecave M, Ollagnier de Choudens S (2009) Native Escherichia coli SufA, coexpressed with SufBCDSE, purifies as a [2Fe-2S] protein and acts as an Fe-S transporter to Fe-S target enzymes. J Am Chem Soc 131:6149–6153

    Article  PubMed  CAS  Google Scholar 

  • Ha JH, McKay DB (1994) ATPase kinetics of recombinant bovine 70 kDa heat shock cognate protein and its amino-terminal ATPase domain. Biochemistry 33:14625–14635

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Heller K (2010) Synopsis. Multiple sulfur acceptors dock at IscS. PLoS Biol 8:e1000353

    Google Scholar 

  • Hesterkamp T, Bukau B (1998) Role of the DnaK and HscA homologs of Hsp70 chaperones in protein folding in E. coli. EMBO J 17:4818–4828

    Article  PubMed  CAS  Google Scholar 

  • Hoff KG, Silberg JJ, Vickery LE (2000) Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proc Natl Acad Sci USA 97:7790–7795

    Article  PubMed  CAS  Google Scholar 

  • Hoff KG, Ta DT, Tapley TL, Silberg JJ, Vickery LE (2002) Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU. J Biol Chem 277, 27353–27359

    Article  PubMed  CAS  Google Scholar 

  • Hoff KG, Cupp-Vickery JR, Vickery LE (2003) Contributions of the LPPVK motif of the iron-sulfur template protein IscU to interactions with the Hsc66-Hsc20 chaperone system. J Biol Chem 278:37582–37589

    Article  PubMed  CAS  Google Scholar 

  • Hsu WM, Lee H, Juan HF, Shih YY, Wang BJ, Pan CY, Jeng YM, Chang HH, Lu MY, Lin KH, Lai HS, Chen WJ, Tsay YG, Liao YF, Hsieh FJ (2008) Identification of GRP75 as an independent favorable prognostic marker of neuroblastoma by a proteomics analysis. Clin Cancer Res 14:6237–6245

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Dizin E, Cowan JA (2008) Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein. J Biol Inorg Chem 13:825–836

    Article  PubMed  CAS  Google Scholar 

  • Huet G, Daffé M, Saves I (2005) Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen’s survival. J Bacteriol 187:6137–6146

    Article  PubMed  CAS  Google Scholar 

  • Huynen MA, Snel B, Bork P, Gibson TJ (2001) The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum Mol Genet 10:2463–2468

    Article  PubMed  CAS  Google Scholar 

  • Iosefson O, Azem A (2010) Reconstitution of the mitochondrial Hsp70 (mortalin)-p53 interaction using purified proteins—identification of additional interacting regions. FEBS Lett 584:1080–1084

    Article  PubMed  CAS  Google Scholar 

  • Jacobson MR, Brigle KE, Bennett LT, Setterquist RA, Wilson MS, Cash VL, Beynon J, Newton WE, Dean DR (1989) Physical and genetic map of the major nif gene cluster from Azotobacter vinelandii. J Bacteriol 171:1017–1027

    PubMed  CAS  Google Scholar 

  • Jensen LT, Culotta VC (2000) Role of Saccharomyces cerevisiae ISA1 and ISA2 in iron homeostasis. Mol Cell Biol 20:3918–3927

    Article  PubMed  CAS  Google Scholar 

  • Jiang J, Lafer EM, Sousa R (2006) Crystallization of a functionally intact Hsc70 chaperone. Acta Crystallogr Sect F Struct Biol Cryst Commun 62:39–43

    Article  PubMed  CAS  Google Scholar 

  • Jin J, Hulette C, Wang Y, Zhang T, Pan C, Wadhwa R, Zhang J (2006) Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics 5:1193–1204

    Article  PubMed  CAS  Google Scholar 

  • Johnson DC, Dean DR, Smith AD, Johnson MK (2005) Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem 74:247–281

    Article  PubMed  CAS  Google Scholar 

  • Kaul SC, Taira K, Pereira-Smith OM, Wadhwa R (2002) Mortalin: present and prospective. Exp Gerontol 37:1157–1164

    Article  PubMed  CAS  Google Scholar 

  • Kaul SC, Deocaris CC, Wadhwa R (2007) Three faces of mortalin: a housekeeper, guardian and killer. Exp Gerontol 42:263–274

    Article  PubMed  CAS  Google Scholar 

  • Kessler D (2006) Enzymatic activation of sulfur for incorporation into biomolecules in prokaryotes. FEMS Microbiol Rev 30:825–840

    Article  PubMed  CAS  Google Scholar 

  • Kim R, Saxena S, Gordon DM, Pain D, Dancis A (2001) J-domain protein, Jac1p, of yeast mitochondria required for iron homeostasis and activity of Fe-S cluster proteins. J Biol Chem 276, 17524–17532

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Füzéry AK, Tonelli M, Ta DT, Westler WM, Vickery LE, Markley JL (2009) Structure and dynamics of the iron-sulfur cluster assembly scaffold protein IscU and its interaction with the cochaperone HscB. Biochemistry 48:6062–6071

    Article  PubMed  CAS  Google Scholar 

  • Kim KD, Chung WH, Kim HJ, Lee KC, Roe JH (2010) Monothiol glutaredoxin Grx5 interacts with Fe-S scaffold proteins Isa1 and Isa2 and supports Fe-S assembly and DNA integrity in mitochondria of fission yeast. Biochem Biophys Res Commun 392:467–472

    Article  PubMed  CAS  Google Scholar 

  • Knieszner H, Schilke B, Dutkiewicz R, D’Silva P, Cheng S, Ohlson M, Craig EA, Marszalek J (2005) Compensation for a defective interaction of the hsp70 ssq1 with the mitochondrial Fe-S cluster scaffold isu. J Biol Chem 280:28966–28972

    Article  PubMed  CAS  Google Scholar 

  • Kuhnke G, Neumann K, Mühlenhoff U, Lill R (2006) Stimulation of the ATPase activity of the yeast mitochondrial ABC transporter Atm1p by thiol compounds. Mol Membr Biol 23:173–184

    Article  PubMed  CAS  Google Scholar 

  • Lange H, Kaut A, Kispal G, Lill R (2000) A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins. Proc Natl Acad Sci USA 97:1050–1055

    Article  PubMed  CAS  Google Scholar 

  • Laufen T, Mayer MP, Beisel C, Klostermeier D, Mogk A, Reinstein J, Bukau B (1999) Mechanism of regulation of hsp70 chaperones by DnaJ cochaperones. Proc Natl Acad Sci USA 96:5452–5457

    Article  PubMed  CAS  Google Scholar 

  • Layer G, Ollagnier-de Choudens S, Sanakis Y, Fontecave M (2006) Iron-sulfur cluster biosynthesis: characterization of Escherichia coli CYaY as an iron donor for the assembly of [2Fe-2S] clusters in the scaffold IscU. J Biol Chem 281:16256–16263

    Article  PubMed  CAS  Google Scholar 

  • Layer G, Gaddam SA, Ayala-Castro CN, Ollagnier-de Choudens S, Lascoux D, Fontecave M, Outten FW (2007) SufE transfers sulfur from SufS to SufB for iron-sulfur cluster assembly. J Biol Chem 282:13342–13350

    Article  PubMed  CAS  Google Scholar 

  • Leidgens S, De Smet S, Foury F (2010) Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet. Hum Mol Genet 19:276–286

    Article  PubMed  CAS  Google Scholar 

  • Li J, Saxena S, Pain D, Dancis A (2001) Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria required for iron homeostasis. J Biol Chem 276:1503–1509

    Article  PubMed  CAS  Google Scholar 

  • Lill R (2009) Function and biogenesis of iron-sulphur proteins. Nature 460:831–838

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lill R, Muhlenhoff U (2005) Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem Sci 30:133–141

    Article  PubMed  CAS  Google Scholar 

  • Lill R, Muhlenhoff U (2006) Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms. Annu Rev Cell Dev Biol 22:457–486

    Article  PubMed  CAS  Google Scholar 

  • Lill R, Dutkiewicz R, Elsässer HP, Hausmann A, Netz DJ, Pierik AJ, Stehling O, Urzica E, Mühlenhoff U (2006) Mechanisms of iron-sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes. Biochim Biophys Acta 1763:652–667

    Article  PubMed  CAS  Google Scholar 

  • Linares GR, Xing W, Govoni KE, Chen ST, Mohan S (2009) Glutaredoxin 5 regulates osteoblast apoptosis by protecting against oxidative stress. Bone 44:795–804

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Krzewska J, Liberek K, Craig EA (2001) Mitochondrial Hsp70 Ssc1: role in protein folding. J Biol Chem 276:6112–6118

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, D’Silva P, Walter W, Marszalek J, Craig EA (2003) Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300:139–141

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Cowan JA (2007) Iron sulfur cluster biosynthesis: human NFU mediates sulfide delivery to ISU in the final step of [2Fe-2S] cluster assembly. Chem Commun 30:3192–31940

    Article  CAS  Google Scholar 

  • Liu Y, Qi W, Cowan JA (2009) Iron-sulfur cluster biosynthesis: functional characterization of the N- and C-terminal domains of human NFU. Biochemistry 48:973–980

    Article  PubMed  CAS  Google Scholar 

  • Loiseau L, Ollagnier-de-Choudens S, Nachin L, Fontecave M, Barras F (2003) Biogenesis of Fe-S cluster by the bacterial Suf system: SufS and SufE form a new type of cysteine desulfurase. J Biol Chem 278:38352–38359

    Article  PubMed  CAS  Google Scholar 

  • Loiseau L, Gerez C, Bekker M, Ollagnier-de Choudens S, Py B, Sanakis Y, Teixeira de Mattos J, Fontecave M, Barras F (2007) ErpA, an iron sulfur (Fe S) protein of the A-type essential for respiratory metabolism in Escherichia coli. Proc Natl Acad Sci USA 104:13626–13631

    Article  PubMed  CAS  Google Scholar 

  • Luo WI, Dizin E, Yoon T, Cowan JA (2010) Kinetic and structural characterization of human mortalin. Protein Expr Purif 72:75–81

    Article  PubMed  CAS  Google Scholar 

  • Lutz T, Westermann B, Neupert W, Herrmann JM (2001) The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria. J Mol Biol 307:815–825

    Article  PubMed  CAS  Google Scholar 

  • Mansy SS, Cowan JA (2004) Iron-sulfur cluster biosynthesis: toward an understanding of cellular machinery and molecular mechanism. Acc Chem Res 37:719–725

    Article  PubMed  CAS  Google Scholar 

  • Mansy SS, Wu G, Surerus KK, Cowan JA (2002) Iron-sulfur cluster biosynthesis. Thermatoga maritima IscU is a structured iron-sulfur cluster assembly protein. J Biol Chem 277:21397–21404

    Article  PubMed  CAS  Google Scholar 

  • Marchenko ND, Zaika A, Moll UM (2000) Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem 275:16202–16212

    Article  PubMed  CAS  Google Scholar 

  • Marquet A, Bui BT, Smith AG, Warren MJ (2007) Iron-sulfur proteins as initiators of radical chemistry. Nat Prod Rep 24:1027–1040

    Article  PubMed  CAS  Google Scholar 

  • Martin W, Russell MJ (2003) On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells. Philos Trans R Soc B-Biol Sci 358:59–83

    Article  CAS  Google Scholar 

  • Miao R, Kim H, Koppolu UM, Ellis EA, Scott RA, Lindahl PA (2009) Biophysical characterization of the iron in mitochondria from Atm1p-depleted Saccharomyces cerevisiae. Biochemistry 48:9556–9568

    Article  PubMed  CAS  Google Scholar 

  • Mihara H, Esaki N (2002) Bacterial cysteine desulfurases: their function and mechanisms. Appl Microbiol Biotechnol 60:12–23

    Article  PubMed  CAS  Google Scholar 

  • Mizzen LA, Kabiling AN, Welch WJ (1991) The two mammalian mitochondrial stress proteins, grp 75 and hsp 58, transiently interact with newly synthesized mitochondrial proteins. Cell Regul 2:165–179

    PubMed  CAS  Google Scholar 

  • Montgomery DL, Morimoto RI, Gierasch LM (1999) Mutations in the substrate binding domain of the Escherichia coli 70 kDa molecular chaperone, DnaK, which alter substrate affinity or interdomain coupling. J Mol Biol 286:915–932

    Article  PubMed  CAS  Google Scholar 

  • Morano KA (2007) New tricks for an old dog: the evolving world of Hsp70. Ann N Y Acad Sci 1113:1–14

    Article  PubMed  CAS  Google Scholar 

  • Mortenson LE, Valentine RC, Carnahan JE (1962) An electron transport factor from Clostridium pasteurianum. Biochem Biophys Res Commun 7:448–452

    Article  PubMed  CAS  Google Scholar 

  • Mühlenhoff 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

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Mühlenhoff 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

    Article  PubMed  CAS  Google Scholar 

  • Nakai Y, Umeda N, Suzuki T, Nakai M, Hayashi H, Watanabe K, Kagamiyama H (2004) Yeast Nfs1p is involved in thio-modification of both mitochondrial and cytoplasmic tRNAs. J Biol Chem 279:12363–12368

    Article  PubMed  CAS  Google Scholar 

  • Nuth M, Cowan JA (2009) Iron-sulfur cluster biosynthesis: characterization of IscU-IscS complex formation and a structural model for sulfide delivery to the [2Fe-2S] assembly site. J Biol Inorg Chem 14:829–839

    Article  PubMed  CAS  Google Scholar 

  • Ollagnier-de-Choudens S, Mattioli T, Takahashi Y, Fontecave M (2001) Iron-sulfur cluster assembly: characterization of IscA and evidence for a specific and functional complex with ferredoxin. J Biol Chem 276:22604–22607

    Article  PubMed  CAS  Google Scholar 

  • Ollagnier-de-Choudens S, Sanakis Y, Fontecave M (2004) SufA/IscA: reactivity studies of a class of scaffold proteins involved in [Fe-S] cluster assembly. J Biol Inorg Chem 9:828–838

    Article  PubMed  CAS  Google Scholar 

  • Outten FW, Wood MJ, Munoz FM, Storz G (2003) The SufE protein and the SufBCD complex enhance SufS cysteine desulfurase activity as part of a sulfur transfer pathway for Fe-S cluster assembly in Escherichia coli. J Biol Chem 278:45713

    Google Scholar 

  • Papanikolaou G, Pantopoulos K (2005) Iron metabolism and toxicity. Toxicol Appl Pharmacol 202:199–211

    Article  PubMed  CAS  Google Scholar 

  • Paris Z, Changmai P, Rubio MA, Zíková A, Stuart KD, Alfonzo JD, Lukes J (2010) The Fe/S cluster assembly protein Isd11 is essential for tRNA thiolation in Trypanosoma brucei. J Biol Chem 285:22394–22402

    Article  PubMed  CAS  Google Scholar 

  • Pelzer W, Mühlenhoff U, Diekert K, Siegmund K, Kispal G, Lill R (2000) Mitochondrial Isa2p plays a crucial role in the maturation of cellular iron-sulfur proteins. FEBS Lett 476:134–139

    Article  PubMed  CAS  Google Scholar 

  • Py B, Barras F (2010) Building Fe-S proteins: bacterial strategies. Nat Rev Microbiol 8:436–446

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Ran Q, Wadhwa R, Kawai R, Kaul SC, Sifers RN, Bick RJ, Smith JR, Pereira-Smith OM (2000) Extra-mitochondrial localization of mortalin/mthsp70/ PBP74/GRP75. Biochem Biophys Res Commun 275:174–179

    Article  PubMed  CAS  Google Scholar 

  • Ranquet C, Ollagnier-de-Choudens S, Loiseau L, Barras F, Fontecave M (2007) Cobalt stress in Escherichia coli. The effect on the iron-sulfur proteins. J Biol Chem 282:30442–30451

    Article  PubMed  CAS  Google Scholar 

  • Rawat S, Stemmler TL (2011) Key players and their role during mitochondrial iron-sulfur cluster biosynthesis. Chemistry 17:746–753

    Article  PubMed  CAS  Google Scholar 

  • Revington M, Zhang Y, Yip GN, Kurochkin AV, Zuiderweg ER (2005) NMR investigations of allosteric processes in a two-domain Thermus thermophilus Hsp70 molecular chaperone. J Mol Biol 349:163–183

    Article  PubMed  CAS  Google Scholar 

  • Richards TA, Van Der Giezen M (2006) Evolution of the Isd11-IscS complex reveals a single alpha-proteobacterial endosymbiosis for all eukaryotes. Mol Biol Evol 23:1341–1344

    Article  PubMed  CAS  Google Scholar 

  • Rincon-Enriquez G, Crété P, Barras F, Py B (2008) Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions. Mol Microbiol 67:1257–1273

    Article  PubMed  CAS  Google Scholar 

  • Rist W, Graf C, Bukau B, Mayer MP (2006) Amide hydrogen exchange reveals conformational changes in hsp70 chaperones important for allosteric regulation. J Biol Chem 281:16493–16501

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez-Manzaneque MT, Tamarit J, Bellí G, Ros J, Herrero E (2002) Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol Biol Cell 13:1109–1121

    Article  PubMed  CAS  Google Scholar 

  • Russell R, Jordan R, McMacken R (1998) Kinetic characterization of the ATPase cycle of the DnaK molecular chaperone. Biochemistry 37:596–607

    Article  PubMed  CAS  Google Scholar 

  • San Pietro A, Lang HM (1958) Photosynthetic pyridine nucleotide reductase. I. Partial purification and properties of the enzyme from spinach. J Biol Chem 231:211–229

    Google Scholar 

  • Schilke B, Voisine C, Beinert H, Craig E (1999) Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 96:10206–10211

    Article  PubMed  CAS  Google Scholar 

  • Schilke B, Williams B, Knieszner H, Pukszta S, D’Silva P, Craig EA, Marszalek J (2006) Evolution of mitochondrial chaperones utilized in Fe-S cluster biogenesis. Curr Biol 16:1660–1665

    Article  PubMed  CAS  Google Scholar 

  • Schmid D, Baici A, Gehring H, Christen P (1994) Kinetics of molecular chaperone action. Science 263:971–973

    Article  PubMed  CAS  Google Scholar 

  • Schmucker S, Martelli A, Colin F, Page A, Wattenhofer-Donzé M, Reutenauer L, Puccio H (2011) Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex. PLoS One 6: e16199

    Google Scholar 

  • Schoenfeld RA, Napoli E, Wong A, Zhan S, Reutenauer L, Morin D, Buckpitt AR, Taroni F, Lonnerdal B, Ristow M, Puccio H, Cortopassi GA (2005) Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. Hum Mol Genet 14:3787–3799

    Article  PubMed  CAS  Google Scholar 

  • Schwartz CJ, Giel JL, Patschkowski T, Luther C, Ruzicka FJ, Beinert H, Kiley PJ (2001) IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins. Proc Natl Acad Sci USA 98:14895–14900

    Article  PubMed  CAS  Google Scholar 

  • Sendra M, Ollagnier de Choudens S, Lascoux D, Sanakis Y, Fontecave M (2007) The SUF iron-sulfur cluster biosynthetic machinery: sulfur transfer from the SUFS-SUFE complex to SUFA. FEBS Lett 581:1362–1368

    Article  PubMed  CAS  Google Scholar 

  • Shan Y, Napoli E, Cortopassi G (2007) Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet 16:929–941

    Article  PubMed  CAS  Google Scholar 

  • Sheftel AD, Lill R (2009) The power plant of the cell is also a smithy: the emerging role of mitochondria in cellular iron homeostasis. Ann Med 41:82–99

    Article  PubMed  CAS  Google Scholar 

  • Sheftel A, Stehling O, Lill R (2010) Iron-sulfur proteins in health and disease. Trends Endocrinol Metab 21:302–314

    Article  PubMed  CAS  Google Scholar 

  • Sheftel AD, Stehling O, Pierik AJ, Elsässer HP, Mühlenhoff U, Webert H, Hobler A, Hannemann F, Bernhardt R, Lill R (2010) Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis. Proc Natl Acad Sci USA 107:11775–11780

    Article  PubMed  CAS  Google Scholar 

  • Shi M, Jin J, Wang Y, Beyer RP, Kitsou E, Albin RL, Gearing M, Pan C, Zhang J (2008) Mortalin: a protein associated with progression of Parkinson disease? J Neuropathol Exp Neurol 67:117–124

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Ghosh MC, Tong WH, Rouault TA (2009) Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Hum Mol Genet 18:3014–3025

    Article  PubMed  CAS  Google Scholar 

  • Shi R, Proteau A, Villarroya M, Moukadiri I, Zhang L, Trempe JF, Matte A, Armengod ME, Cygler M (2010) Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS protein-protein interactions. PLoS Biol 8:e1000354

    Google Scholar 

  • Sichting M, Mokranjac D et al (2005) Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1. EMBO J 24:1046–1056

    Article  PubMed  CAS  Google Scholar 

  • Silberg JJ, Vickery LE (2000) Kinetic characterization of the ATPase cycle of the molecular chaperone Hsc66 from Escherichia coli. J Biol Chem 275:7779–7786

    Article  PubMed  CAS  Google Scholar 

  • Silberg JJ, Hoff KG et al (1998) The Hsc66-Hsc20 chaperone system in Escherichia coli: chaperone activity and interactions with the DnaK-DnaJ-grpE system. J Bacteriol 180:6617–6624

    PubMed  CAS  Google Scholar 

  • Silberg JJ, Hoff KG et al (2001) The Fe/S assembly protein IscU behaves as a substrate for the molecular chaperone Hsc66 from Escherichia coli. J Biol Chem 276:1696–1700

    Article  PubMed  CAS  Google Scholar 

  • Silberg JJ, Tapley TL et al (2004) Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU. J Biol Chem 279:53924–53931

    Article  PubMed  CAS  Google Scholar 

  • Smith AD, Frazzon J et al (2005) Role of conserved cysteines in mediating sulfur transfer from IscS to IscU. FEBS Lett 579:5236–5240

    Article  PubMed  CAS  Google Scholar 

  • Stemmler TL, Lesuisse E et al (2010) Frataxin and mitochondrial FeS cluster biogenesis. J Biol Chem 285, 26737–26743

    Article  PubMed  CAS  Google Scholar 

  • Subramanian P, Rodrigues AV et al (2011) Iron chaperones for mitochondrial Fe-S cluster biosynthesis and ferritin iron storage. Curr Opin Chem Biol 15:312-318 (Jan 31 issue)

    Article  PubMed  CAS  Google Scholar 

  • Sutak R, Dolezal P et al (2004) Mitochondrial-type assembly of FeS centers in the hydrogenosomes of the amitochondriate eukaryote Trichomonas vaginalis. Proc Natl Acad Sci USA 101:10368–10373

    Article  PubMed  CAS  Google Scholar 

  • Swain JF, Dinler G et al (2007) Hsp70 chaperone ligands control domain association via an allosteric mechanism mediated by the interdomain linker. Mol Cell 26:27–39

    Article  PubMed  CAS  Google Scholar 

  • Tachezy JL, Sanchez B et al (2001) Mitochondrial type iron-sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS. Mol Biol Evol 18:1919–1928

    Article  PubMed  CAS  Google Scholar 

  • Takahashi Y, Nakamura M (1999) Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli. J Biochem 126:917–926

    Article  PubMed  CAS  Google Scholar 

  • Takahashi Y, Tokumoto U (2002) A third bacterial system for the assembly of iron-sulfur clusters with homologs in archaea and plastids. J Biol Chem 277:28380–28383

    Article  PubMed  CAS  Google Scholar 

  • Takano S, Wadhwa R et al (1997) Elevated levels of mortalin expression in human brain tumors. Exp Cell Res 237:38–45

    Article  PubMed  CAS  Google Scholar 

  • Takashima M, Kuramitsu Y et al (2003) Proteomic profiling of heat shock protein 70 family members as biomarkers for hepatitis C virus-related hepatocellular carcinoma. Proteomics 3:2487–2493

    Article  PubMed  CAS  Google Scholar 

  • Tapley TL, Vickery LE (2004) Preferential substrate binding orientation by the molecular chaperone HscA. J Biol Chem 279:28435–28442

    Article  PubMed  CAS  Google Scholar 

  • Tapley TL, Cupp-Vickery JR et al (2006) Structural determinants of HscA peptide-binding specificity. Biochemistry 45:8058–8066

    Article  PubMed  CAS  Google Scholar 

  • Tokumoto U, Takahashi Y (2001) Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins. J Biochem 130:63–71

    Article  PubMed  CAS  Google Scholar 

  • Tokumoto U, Nomura S et al (2002) Network of protein-protein interactions among iron-sulfur cluster assembly proteins in Escherichia coli. J Biochem 131:713–719

    Article  PubMed  CAS  Google Scholar 

  • Tokumoto U, Kitamura S et al (2004) Interchangeability and distinct properties of bacterial Fe-S cluster assembly systems: functional replacement of the isc and suf operons in Escherichia coli with the nifSU-like operon from Helicobacter pylori. J Biochem 136:199–209

    Article  PubMed  CAS  Google Scholar 

  • Tong WH, Rouault TA (2006) Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab 3:199–210

    Article  PubMed  CAS  Google Scholar 

  • Tsai CL, Barondeau DP (2010) Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex. Biochemistry 49:9132–9139

    Article  PubMed  CAS  Google Scholar 

  • Uhrigshardt H, Singh A, Kovtunovych G, Ghosh M, Rouault TA (2010) Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis. Hum Mol Genet 19:3816–3834

    Article  PubMed  CAS  Google Scholar 

  • Vickery LE, Cupp-Vickery JR (2007) Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur protein maturation. Crit Rev Biochem Mol Biol 42:95–111

    Article  PubMed  CAS  Google Scholar 

  • Vickery LE, Silberg JJ, Ta DT (1997) Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from Escherichia coli. Protein Sci 6:1047–1056

    Article  PubMed  CAS  Google Scholar 

  • Vogel M, Bukau B, Mayer MP (2006a) Allosteric regulation of Hsp70 chaperones by a proline switch. Mol Cell 21:359–367

    Article  CAS  Google Scholar 

  • Vogel M, Mayer MP, Bukau B (2006b) Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. J Biol Chem 281:38705–38711

    Article  CAS  Google Scholar 

  • Voisine C, Schilke B, Ohlson M, Beinert H, Marszalek J, Craig EA (2000) Role of the mitochondrial Hsp70 s, Ssc1 and Ssq1, in the maturation of Yfh1. Mol Cell Biol 20:3677–3684

    Article  PubMed  CAS  Google Scholar 

  • Wachtershauser G (2007) On the chemistry and evolution of the pioneer organism. Chem Biodivers 4:584–602

    Article  PubMed  Google Scholar 

  • Wadhwa R, Takano S, Robert M, Yoshida A, Nomura H, Reddel RR, Mitsui Y, Kaul SC (1998) Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member. J Biol Chem 273:29586–29591

    Article  PubMed  CAS  Google Scholar 

  • Wadhwa R, Taira K, Kaul SC (2002) An Hsp70 family chaperone, mortalin/mthsp70/PBP74/Grp75: what, when, and where? Cell Stress Chaperones 7:309–316

    Article  PubMed  CAS  Google Scholar 

  • Wadhwa R, Takano S, Kaur K, Deocaris CC, Pereira-Smith OM, Reddel RR, Kaul SC (2006) Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis. Int J Cancer 118:2973–2980

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Craig EA (2008) Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu. J Biol Chem 283:12674–12679

    Article  PubMed  CAS  Google Scholar 

  • Wiedemann N, Urzica E, Guiard B, Müller H, Lohaus C, Meyer HE, Ryan MT, Meisinger C, Mühlenhoff U, Lill R, Pfanner N (2006) Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins. EMBO J 25:184–195

    Article  PubMed  CAS  Google Scholar 

  • Wilson RB (2006) Iron dysregulation in Friedreich ataxia. Semin Pediatr Neurol 13:166–175

    Article  PubMed  Google Scholar 

  • Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ, Dooley K, Davidson AJ, Schmid B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI, Tübingen (2000) Screen Consortium (2005) Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436:1035–1039

    Article  CAS  Google Scholar 

  • Wollers S, Layer G, Garcia-Serres R, Signor L, Clemancey M, Latour JM, Fontecave M, Ollagnier de Choudens S (2010) Iron-sulfur (Fe-S) cluster assembly: the SufBCD complex is a new type of Fe-S scaffold with a flavin redox cofactor. J Biol Chem 285:23331–23341

    Article  PubMed  CAS  Google Scholar 

  • Wu SP, Cowan JA (2003) Iron-sulfur cluster biosynthesis. A comparative kinetic analysis of native and Cys-substituted ISA-mediated [2Fe-2S]2+ cluster transfer to an apoferredoxin target. Biochemistry 42:5784–5791

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Mansy SS, Hemann C, Hille R, Surerus KK, Cowan JA (2002a) Iron-sulfur cluster biosynthesis: characterization of Schizosaccharomyces pombe Isa1. J Biol Inorg Chem 7:526–532

    Article  CAS  Google Scholar 

  • Wu G, Mansy SS, Wu Sp SP, Surerus KK, Foster MW, Cowan JA (2002b) Characterization of an iron-sulfur cluster assembly protein (ISU1) from Schizosaccharomyces pombe. Biochemistry 41:5024–5032

    Article  CAS  Google Scholar 

  • Wu SP, Wu G, Surerus KK, Cowan JA (2002c) Iron-sulfur cluster biosynthesis. Kinetic analysis of [2Fe-2S] cluster transfer from holo ISU to apo Fd: role of redox chemistry and a conserved aspartate. Biochemistry 41:8876–8885

    Article  CAS  Google Scholar 

  • Wu SP, Mansy SS, Cowan JA (2005) Iron-sulfur cluster biosynthesis. Molecular chaperone DnaK promotes IscU-bound [2Fe-2S] cluster stability and inhibits cluster transfer activity. Biochemistry 44:4284–4293

    Article  PubMed  CAS  Google Scholar 

  • Xu XM, Moller SG (2011) Iron-sulfur clusters: biogenesis, molecular mechanisms, and their functional significance. Antioxid Redox Signal 15:271–307

    Article  PubMed  CAS  Google Scholar 

  • Ye H, Rouault TA (2010) Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 49:4945–4956

    Article  PubMed  CAS  Google Scholar 

  • Ye H, Jeong SY, Ghosh MC, Kovtunovych G, Silvestri L, Ortillo D, Uchida N, Tisdale J, Camaschella C, Rouault TA (2010) Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest 120:1749–1761

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Zhai P, Stanworth C, Liu S, Silberg JJ (2008) The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis. J Biol Chem 283:26098–26106

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Lyver ER, Knight SA, Lesuisse E, Dancis A (2005) Frataxin and mitochondrial carrier proteins, Mrs3p and Mrs4p, cooperate in providing iron for heme synthesis. J Biol Chem 280:19794–19807

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Lyver ER, Knight SA, Pain D, Lesuisse E, Dancis A (2006) Mrs3p, Mrs4p, and frataxin provide iron for Fe-S cluster synthesis in mitochondria. J Biol Chem 281:22493–22502

    Article  PubMed  CAS  Google Scholar 

  • Zheng L, White RH, Cash VL, Dean DR (1994) Mechanism for the desulfurization of L-cysteine catalyzed by the nifS gene product. Biochemistry 33:4714–4720

    Article  PubMed  CAS  Google Scholar 

  • Zheng L, Cash VL, Flint DH, Dean DR (1998) Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J Biol Chem 273:13264–13272

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the National Institutes of Health for generous support of this research through grant # AI072443.

Author information

Authors and Affiliations

  1. Chemistry, The Ohio State University, 43210, Columbus, Ohio, USA

    James A. Cowan

  2. Evans Laboratory of Chemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA

    James A. Cowan

  3. Ohio State Biochemistry Program, The Ohio State University, 43210, Columbus, OH, USA

    Wen-I Luo

Authors
  1. Wen-I Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James A. Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James A. Cowan .

Editor information

Editors and Affiliations

  1. National Institute of Advanced Industria, Central 4, Higashi 1 -1-1, Tsukuba, 305 8566, Ibaraki, Japan

    Sunil C. Kaul

  2. Science & Technology (AIST), National Insitute of Advanced Industrial, Central 4, Higashi 1-1-1, Tsukuba, 305-8562, Ibaraki, Japan

    Renu Wadhwa

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Luo, WI., Cowan, J.A. (2012). The Role of Mortalin in Iron Homeostasis. In: Kaul, S., Wadhwa, R. (eds) Mortalin Biology: Life, Stress and Death. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3027-4_3

Download citation

Publish with us

Policies and ethics

Search

Navigation