Advertisement

Iron-Sulfur Protein Assembly in Human Cells

  • Prasenjit Prasad Saha
  • Vinaya Vishwanathan
  • Kondalarao Bankapalli
  • Patrick D’Silva
Chapter
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 174)

Abstract

Iron-sulfur (Fe-S) clusters serve as a fundamental inorganic constituent of living cells ranging from bacteria to human. The importance of Fe-S clusters is underscored by their requirement as a co-factor for the functioning of different enzymes and proteins. The biogenesis of Fe-S cluster is a highly coordinated process which requires specialized cellular machinery. Presently, understanding of Fe-S cluster biogenesis in human draws meticulous attention since defects in the biogenesis process result in development of multiple diseases with unresolved solutions. Mitochondrion is the major cellular compartment of Fe-S cluster biogenesis, although cytosolic biogenesis machinery has been reported in eukaryotes, including in human. The core biogenesis pathway comprises two steps. The process initiates with the assembly of Fe-S cluster on a platform scaffold protein in the presence of iron and sulfur donor proteins. Subsequent process is the transfer and maturation of the cluster to a bonafide target protein. Human Fe-S cluster biogenesis machinery comprises the mitochondrial iron-sulfur cluster (ISC) assembly and export system along with the cytosolic Fe-S cluster assembly (CIA) machinery. Impairment in the Fe-S cluster machinery components results in cellular dysfunction leading to various mitochondrial pathophysiological consequences. The current review highlights recent developments and understanding in the domain of Fe-S cluster assembly biology in higher eukaryotes, particularly in human cells.

Keywords

Chaperones Fe-S biogenesis Iron-sulfur clusters Iron-transfer Mitochondria 

Notes

Acknowledgements

We express our sincere gratitude to the members of our group for the critical reading and review of the manuscript. We greatly acknowledge Department of Science and Technology for Swarnajayanthi fellowship (Grant ID: DST/SJF/LSA-01/2011–2012), DBT-IISc partnership programme (Grant ID: DBT/BF/PR/INS/2011-12/IISc), DST-FIST programme (Grant ID: SR/FST/LSII-544 023/2009), and UGC-CAS SAP-II programme (Grant ID: UGC LT. No. F. 5-2/2012. SAP-II) to P.D.S. We also acknowledge CSIR-India for SRF to P.P.S and K.B. We apologize to all colleagues and fellow researchers of the related domain whose original work could not be discussed or cited owing to length limitations.

References

  1. Acquaviva F, De Biase I, Nezi L, Ruggiero G, Tatangelo F, Pisano C, Monticelli A, Garbi C, Acquaviva AM, Cocozza S (2005) Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2. J Cell Sci 118(17):3917–3924. doi: 10.1242/jcs.02516CrossRefPubMedGoogle Scholar
  2. Agar JN, Krebs C, Frazzon J, Huynh BH, Dean DR, Johnson MK (2000) IscU as a scaffold for iron-sulfur cluster biosynthesis: sequential assembly of [2Fe-2S] and [4Fe-4S] clusters in IscU. Biochemistry 39(27):7856–7862CrossRefGoogle Scholar
  3. Ajit Bolar N, Vanlander AV, Wilbrecht C, Van der Aa N, Smet J, De Paepe B, Vandeweyer G, Kooy F, Eyskens F, De Latter E, Delanghe G, Govaert P, Leroy JG, Loeys B, Lill R, Van Laer L, Van Coster R (2013) Mutation of the iron-sulfur cluster assembly gene IBA57 causes severe myopathy and encephalopathy. Hum Mol Genet 22(13):2590–2602. doi: 10.1093/hmg/ddt107CrossRefPubMedGoogle Scholar
  4. Al-Hassnan ZN, Al-Dosary M, Alfadhel M, Faqeih EA, Alsagob M, Kenana R, Almass R, Al-Harazi OS, Al-Hindi H, Malibari OI, Almutari FB, Tulbah S, Alhadeq F, Al-Sheddi T, Alamro R, AlAsmari A, Almuntashri M, Alshaalan H, Al-Mohanna FA, Colak D, Kaya N (2015) ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder. J Med Genet 52(3):186–194. doi: 10.1136/jmedgenet-2014-102592CrossRefPubMedGoogle Scholar
  5. Allen S, Balabanidou V, Sideris DP, Lisowsky T, Tokatlidis K (2005) Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J Mol Biol 353(5):937–944. doi: 10.1016/j.jmb.2005.08.049CrossRefPubMedGoogle Scholar
  6. Aloria K, Schilke B, Andrew A, Craig EA (2004) Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo. EMBO Rep 5(11):1096–1101. doi: 10.1038/sj.embor.7400272CrossRefPubMedPubMedCentralGoogle Scholar
  7. Amick J, Schlanger SE, Wachnowsky C, Moseng MA, Emerson CC, Dare M, Luo WI, Ithychanda SS, Nix JC, Cowan JA, Page RC, Misra S (2014) Crystal structure of the nucleotide-binding domain of mortalin, the mitochondrial Hsp70 chaperone. Protein Sci 23(6):833–842. doi: 10.1002/pro.2466CrossRefPubMedPubMedCentralGoogle Scholar
  8. Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800(8):783–792. doi: 10.1016/j.bbagen.2010.02.005CrossRefPubMedGoogle Scholar
  9. Ayala-Castro C, Saini A, Outten FW (2008) Fe-S cluster assembly pathways in bacteria. Microbiol Mol Biol Rev 72(1):110–125. doi: 10.1128/MMBR.00034-07. Table of ContentsCrossRefPubMedPubMedCentralGoogle Scholar
  10. Baker PR 2nd, Friederich MW, Swanson MA, Shaikh T, Bhattacharya K, Scharer GH, Aicher J, Creadon-Swindell G, Geiger E, KN ML, Lee WT, Deshpande C, Freckmann ML, Shih LY, Wasserstein M, Rasmussen MB, Lund AM, Procopis P, Cameron JM, Robinson BH, Brown GK, Brown RM, Compton AG, Dieckmann CL, Collard R, Coughlin CR 2nd, Spector E, Wempe MF, Van Hove JL (2014) Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. Brain 137(2):366–379. doi: 10.1093/brain/awt328CrossRefPubMedGoogle Scholar
  11. Balk J, Lobreaux S (2005) Biogenesis of iron-sulfur proteins in plants. Trends Plant Sci 10(7):324–331. doi: 10.1016/j.tplants.2005.05.002CrossRefPubMedGoogle Scholar
  12. 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(10):2105–2115. doi: 10.1038/sj.emboj.7600216CrossRefPubMedPubMedCentralGoogle Scholar
  13. Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K (2012) An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc 134(3):1442–1445. doi: 10.1021/ja209881fCrossRefPubMedGoogle Scholar
  14. Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Giachetti A, Jaiswal D, Mikolajczyk M, Piccioli M, Winkelmann J (2013) Molecular view of an electron transfer process essential for iron-sulfur protein biogenesis. Proc Natl Acad Sci U S A 110(18):7136–7141. doi: 10.1073/pnas.1302378110CrossRefPubMedPubMedCentralGoogle Scholar
  15. Banci L, Brancaccio D, Ciofi-Baffoni S, Del Conte R, Gadepalli R, Mikolajczyk M, Neri S, Piccioli M, Winkelmann J (2014) [2Fe-2S] cluster transfer in iron-sulfur protein biogenesis. Proc Natl Acad Sci U S A 111(17):6203–6208. doi: 10.1073/pnas.1400102111CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bandyopadhyay S, Chandramouli K, Johnson MK (2008a) Iron-sulfur cluster biosynthesis. Biochem Soc Trans 36(6):1112–1119. doi: 10.1042/BST0361112CrossRefPubMedPubMedCentralGoogle Scholar
  17. Bandyopadhyay S, Gama F, Molina-Navarro MM, Gualberto JM, Claxton R, Naik SG, Huynh BH, Herrero E, Jacquot JP, Johnson MK, Rouhier N (2008b) Chloroplast monothiol glutaredoxins as scaffold proteins for the assembly and delivery of [2Fe-2S] clusters. EMBO J 27(7):1122–1133. doi: 10.1038/emboj.2008.50CrossRefPubMedPubMedCentralGoogle Scholar
  18. Beilschmidt LK, Puccio HM (2014) Mammalian Fe-S cluster biogenesis and its implication in disease. Biochimie 100:48–60. doi: 10.1016/j.biochi.2014.01.009CrossRefPubMedGoogle Scholar
  19. Beinert H (2000) Iron-sulfur proteins: ancient structures, still full of surprises. J Biol Inorg Chem 5(1):2–15CrossRefGoogle Scholar
  20. Beinert H, Kennedy MC (1993) Aconitase, a two-faced protein: enzyme and iron regulatory factor. FASEB J 7(15):1442–1449CrossRefGoogle Scholar
  21. Beinert H, Kiley PJ (1999) Fe-S proteins in sensing and regulatory functions. Curr Opin Chem Biol 3(2):152–157. doi: 10.1016/S1367-5931(99)80027-1CrossRefPubMedGoogle Scholar
  22. Beinert H, Holm RH, Munck E (1997) Iron-sulfur clusters: nature’s modular, multipurpose structures. Science 277(5326):653–659CrossRefGoogle Scholar
  23. Bekri S, Kispal G, Lange H, Fitzsimons E, Tolmie J, Lill R, Bishop DF (2000) Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood 96(9):3256–3264PubMedGoogle Scholar
  24. Biederbick A, Stehling O, Rosser R, Niggemeyer B, Nakai Y, Elsasser HP, Lill R (2006) Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation. Mol Cell Biol 26(15):5675–5687. doi: 10.1128/MCB.00112-06CrossRefPubMedPubMedCentralGoogle Scholar
  25. Bitto E, Bingman CA, Bittova L, Kondrashov DA, Bannen RM, Fox BG, Markley JL, Phillips GN Jr (2008) Structure of human J-type co-chaperone HscB reveals a tetracysteine metal-binding domain. J Biol Chem 283(44):30184–30192. doi: 10.1074/jbc.M804746200CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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(48):12795–12801. doi: 10.1021/bi801565jCrossRefPubMedGoogle Scholar
  27. Bonomi F, Iametti S, Morleo A, Ta D, Vickery LE (2011) Facilitated transfer of IscU-[2Fe2S] clusters by chaperone-mediated ligand exchange. Biochemistry 50(44):9641–9650. doi: 10.1021/bi201123zCrossRefPubMedGoogle Scholar
  28. Bridwell-Rabb J, Fox NG, Tsai CL, Winn AM, Barondeau DP (2014) Human frataxin activates Fe-S cluster biosynthesis by facilitating sulfur transfer chemistry. Biochemistry 53(30):4904–4913. doi: 10.1021/bi500532eCrossRefPubMedPubMedCentralGoogle Scholar
  29. Brzoska K, Meczynska S, Kruszewski M (2006) Iron-sulfur cluster proteins: electron transfer and beyond. Acta Biochim Pol 53(4):685–691PubMedGoogle Scholar
  30. Buckel W, Hetzel M, Kim J (2004) ATP-driven electron transfer in enzymatic radical reactions. Curr Opin Chem Biol 8(5):462–467. doi: 10.1016/j.cbpa.2004.07.001CrossRefPubMedGoogle Scholar
  31. Bych K, Kerscher S, Netz DJ, Pierik AJ, Zwicker K, Huynen MA, Lill R, Brandt U, Balk J (2008) The iron-sulphur protein Ind1 is required for effective complex I assembly. EMBO J 27(12):1736–1746. doi: 10.1038/emboj.2008.98CrossRefPubMedPubMedCentralGoogle Scholar
  32. Cai K, Frederick RO, Kim JH, Reinen NM, Tonelli M, Markley JL (2013) Human mitochondrial chaperone (mtHSP70) and cysteine desulfurase (NFS1) bind preferentially to the disordered conformation, whereas co-chaperone (HSC20) binds to the structured conformation of the iron-sulfur cluster scaffold protein (ISCU). J Biol Chem 288(40):28755–28770. doi: 10.1074/jbc.M113.482042CrossRefPubMedPubMedCentralGoogle Scholar
  33. Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas M, Guiducci C, Bruno DL, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR, Mootha VK (2010) High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet 42(10):851–858. doi: 10.1038/ng.659CrossRefPubMedPubMedCentralGoogle Scholar
  34. Camaschella C, Campanella A, De Falco L, Boschetto L, Merlini R, Silvestri L, Levi S, Iolascon A (2007) The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood 110(4):1353–1358. doi: 10.1182/blood-2007-02-072520CrossRefPubMedGoogle Scholar
  35. Cameron JM, Janer A, Levandovskiy V, Mackay N, Rouault TA, Tong WH, Ogilvie I, Shoubridge EA, Robinson BH (2011) Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. Am J Hum Genet 89(4):486–495. doi: 10.1016/j.ajhg.2011.08.011CrossRefPubMedPubMedCentralGoogle Scholar
  36. Cavadini P, Biasiotto G, Poli M, Levi S, Verardi R, Zanella I, Derosas M, Ingrassia R, Corrado M, Arosio P (2007) RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload. Blood 109(8):3552–3559. doi: 10.1182/blood-2006-08-041632CrossRefPubMedGoogle Scholar
  37. Chandramouli K, Johnson MK (2006) HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 45(37):11087–11095. doi: 10.1021/bi061237wCrossRefPubMedPubMedCentralGoogle Scholar
  38. Chandramouli K, Unciuleac MC, Naik S, Dean DR, Huynh BH, Johnson MK (2007) Formation and properties of [4Fe-4S] clusters on the IscU scaffold protein. Biochemistry 46(23):6804–6811. doi: 10.1021/bi6026659CrossRefPubMedGoogle Scholar
  39. 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 U S A 99(19):12321–12326. doi: 10.1073/pnas.192449599CrossRefPubMedPubMedCentralGoogle Scholar
  40. Colin F, Martelli A, Clemancey M, Latour JM, Gambarelli S, Zeppieri L, Birck C, Page A, Puccio H, Ollagnier de Choudens S (2012) Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly. J Am Chem Soc 135(2):733–740. doi: 10.1021/ja308736eCrossRefGoogle Scholar
  41. Condo I, Ventura N, Malisan F, Tomassini B, Testi R (2006) A pool of extramitochondrial frataxin that promotes cell survival. J Biol Chem 281(24):16750–16756. doi: 10.1074/jbc.M511960200CrossRefPubMedGoogle Scholar
  42. Condo I, Malisan F, Guccini I, Serio D, Rufini A, Testi R (2010) Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin. Hum Mol Genet 19(7):1221–1229. doi: 10.1093/hmg/ddp592CrossRefPubMedGoogle Scholar
  43. Corbin MV, Rockx DA, Oostra AB, Joenje H, Dorsman JC (2015) The iron-sulfur cluster assembly network component NARFL is a key element in the cellular defense against oxidative stress. Free Radic Biol Med 89:863–872. doi: 10.1016/j.freeradbiomed.2015.08.026CrossRefPubMedGoogle Scholar
  44. Cory SA, Van Vranken JG, Brignole EJ, Patra S, Winge DR, Drennan CL, Rutter J, Barondeau DP (2017) Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. Proc Natl Acad Sci U S A 114(27):E5325–E5334. doi: 10.1073/pnas.1702849114CrossRefPubMedPubMedCentralGoogle Scholar
  45. Craig EA, Marszalek J (2002) A specialized mitochondrial molecular chaperone system: a role in formation of Fe/S centers. Cell Mol Life Sci 59(10):1658–1665CrossRefGoogle Scholar
  46. Cupp-Vickery JR, Urbina H, Vickery LE (2003) Crystal structure of IscS, a cysteine desulfurase from Escherichia coli. J Mol Biol 330(5):1049–1059CrossRefGoogle Scholar
  47. Cupp-Vickery JR, Silberg JJ, Ta DT, Vickery LE (2004) Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli. J Mol Biol 338(1):127–137. doi: 10.1016/j.jmb.2004.02.027CrossRefPubMedGoogle Scholar
  48. Dai S, Schwendtmayer C, Schurmann P, Ramaswamy S, Eklund H (2000) Redox signaling in chloroplasts: cleavage of disulfides by an iron-sulfur cluster. Science 287(5453):655–658CrossRefGoogle Scholar
  49. Dailey HA (2002) Terminal steps of haem biosynthesis. Biochem Soc Trans 30(4):590–595CrossRefGoogle Scholar
  50. Debray FG, Stumpfig C, Vanlander AV, Dideberg V, Josse C, Caberg JH, Boemer F, Bours V, Stevens R, Seneca S, Smet J, Lill R, van Coster R (2015) Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy. J Inherit Metab Dis 38(6):1147–1153. doi: 10.1007/s10545-015-9857-1CrossRefPubMedGoogle Scholar
  51. Di Fonzo A, Ronchi D, Lodi T, Fassone E, Tigano M, Lamperti C, Corti S, Bordoni A, Fortunato F, Nizzardo M, Napoli L, Donadoni C, Salani S, Saladino F, Moggio M, Bresolin N, Ferrero I, Comi GP (2009) The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency. Am J Hum Genet 84(5):594–604. doi: 10.1016/j.ajhg.2009.04.004CrossRefPubMedPubMedCentralGoogle Scholar
  52. Drysdale J, Arosio P, Invernizzi R, Cazzola M, Volz A, Corsi B, Biasiotto G, Levi S (2002) Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis 29(3):376–383CrossRefGoogle Scholar
  53. 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(32):29719–29727. doi: 10.1074/jbc.M303527200CrossRefPubMedGoogle Scholar
  54. 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(28):29167–29174. doi: 10.1074/jbc.M402947200CrossRefPubMedGoogle Scholar
  55. Dutkiewicz R, Marszalek J, Schilke B, Craig EA, Lill R, Muhlenhoff U (2006) The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. J Biol Chem 281(12):7801–7808. doi: 10.1074/jbc.M513301200CrossRefPubMedGoogle Scholar
  56. Farhan SM, Wang J, Robinson JF, Lahiry P, Siu VM, Prasad C, Kronick JB, Ramsay DA, Rupar CA, Hegele RA (2014) Exome sequencing identifies NFS1 deficiency in a novel Fe-S cluster disease, infantile mitochondrial complex II/III deficiency. Mol Genet Genomic Med 2(1):73–80. doi: 10.1002/mgg3.46CrossRefPubMedGoogle Scholar
  57. Ferrer-Cortes X, Font A, Bujan N, Navarro-Sastre A, Matalonga L, Arranz JA, Riudor E, del Toro M, Garcia-Cazorla A, Campistol J, Briones P, Ribes A, Tort F (2012) Protein expression profiles in patients carrying NFU1 mutations. Contribution to the pathophysiology of the disease. J Inherit Metab Dis 36(5):841–847. doi: 10.1007/s10545-012-9565-zCrossRefPubMedGoogle Scholar
  58. Fontecave M, Ollagnier-de-Choudens S (2008) Iron-sulfur cluster biosynthesis in bacteria: mechanisms of cluster assembly and transfer. Arch Biochem Biophys 474(2):226–237. doi: 10.1016/j.abb.2007.12.014CrossRefPubMedGoogle Scholar
  59. Fontecave M, Choudens SO, Py B, Barras F (2005) Mechanisms of iron-sulfur cluster assembly: the SUF machinery. J Biol Inorg Chem 10(7):713–721. doi: 10.1007/s00775-005-0025-1CrossRefPubMedGoogle Scholar
  60. Fox NG, Chakrabarti M, McCormick SP, Lindahl PA, Barondeau DP (2015a) The human iron-sulfur assembly complex catalyzes the synthesis of [2Fe-2S] clusters on ISCU2 that can be transferred to acceptor molecules. Biochemistry 54(25):3871–3879. doi: 10.1021/bi5014485CrossRefPubMedPubMedCentralGoogle Scholar
  61. Fox NG, Das D, Chakrabarti M, Lindahl PA, Barondeau DP (2015b) Frataxin accelerates [2Fe-2S] cluster formation on the human Fe-S assembly complex. Biochemistry 54(25):3880–3889. doi: 10.1021/bi5014497CrossRefPubMedPubMedCentralGoogle Scholar
  62. Frazzon J, Dean DR (2003) Formation of iron-sulfur clusters in bacteria: an emerging field in bioinorganic chemistry. Curr Opin Chem Biol 7(2):166–173CrossRefGoogle Scholar
  63. Friemel M, Marelja Z, Li K, Leimkuhler S (2017) The N-terminus of iron-sulfur cluster assembly factor ISD11 is crucial for subcellular targeting and interaction with l-cysteine desulfurase NFS1. Biochemistry 56(12):1797–1808. doi: 10.1021/acs.biochem.6b01239CrossRefPubMedGoogle Scholar
  64. Gari K, Leon Ortiz AM, Borel V, Flynn H, Skehel JM, Boulton SJ (2012) MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science 337(6091):243–245. doi: 10.1126/science.1219664CrossRefPubMedGoogle Scholar
  65. 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(4):897–907. doi: 10.1006/jmbi.1999.3294CrossRefPubMedGoogle Scholar
  66. Gelling C, Dawes IW, Richhardt N, Lill R, Muhlenhoff U (2008) Mitochondrial Iba57p is required for Fe/S cluster formation on aconitase and activation of radical SAM enzymes. Mol Cell Biol 28(5):1851–1861. doi: 10.1128/MCB.01963-07CrossRefPubMedGoogle Scholar
  67. 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(9):906–911. doi: 10.1038/sj.embor.embor918CrossRefPubMedPubMedCentralGoogle Scholar
  68. 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 proteins. Mol Cell Biol 24(11):4848–4857. doi: 10.1128/MCB.24.11.4848-4857.2004CrossRefPubMedPubMedCentralGoogle Scholar
  69. Goswami AV, Chittoor B, D’Silva P (2010) Understanding the functional interplay between mammalian mitochondrial Hsp70 chaperone machine components. J Biol Chem 285(25):19472–19482. doi: 10.1074/jbc.M110.105957CrossRefPubMedPubMedCentralGoogle Scholar
  70. Goswami AV, Samaddar M, Sinha D, Purushotham J, D’Silva P (2012) Enhanced J-protein interaction and compromised protein stability of mtHsp70 variants lead to mitochondrial dysfunction in Parkinson’s disease. Hum Mol Genet 21(15):3317–3332. doi: 10.1093/hmg/dds162CrossRefPubMedPubMedCentralGoogle Scholar
  71. Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069. doi: 10.1146/annurev.bi.54.070185.005055CrossRefPubMedGoogle Scholar
  72. Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts: molecular control of mammalian iron metabolism. Cell 117(3):285–297CrossRefGoogle Scholar
  73. Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142(1):24–38. doi: 10.1016/j.cell.2010.06.028CrossRefPubMedGoogle Scholar
  74. Invernizzi F, Ardissone A, Lamantea E, Garavaglia B, Zeviani M, Farina L, Ghezzi D, Moroni I (2014) Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations. Front Genet 5:412. doi: 10.3389/fgene.2014.00412CrossRefPubMedPubMedCentralGoogle Scholar
  75. Jarrett JT (2005) The novel structure and chemistry of iron-sulfur clusters in the adenosylmethionine-dependent radical enzyme biotin synthase. Arch Biochem Biophys 433(1):312–321. doi: 10.1016/j.abb.2004.10.003CrossRefPubMedGoogle Scholar
  76. 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(7):1193–1204. doi: 10.1074/mcp.M500382-MCP200CrossRefPubMedGoogle Scholar
  77. Johansson C, Roos AK, Montano SJ, Sengupta R, Filippakopoulos P, Guo K, von Delft F, Holmgren A, Oppermann U, Kavanagh KL (2011) The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. Biochem J 433(2):303–311. doi: 10.1042/BJ20101286CrossRefPubMedGoogle Scholar
  78. Johnson DC, Dean DR, Smith AD, Johnson MK (2005) Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem 74:247–281. doi: 10.1146/annurev.biochem.74.082803.133518CrossRefPubMedGoogle Scholar
  79. Kaiser JT, Clausen T, Bourenkow GP, Bartunik HD, Steinbacher S, Huber R (2000) Crystal structure of a NifS-like protein from Thermotoga maritima: implications for iron sulphur cluster assembly. J Mol Biol 297(2):451–464. doi: 10.1006/jmbi.2000.3581CrossRefPubMedGoogle Scholar
  80. Kampinga HH, Craig EA (2010) The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 11(8):579–592. doi: 10.1038/nrm2941CrossRefPubMedPubMedCentralGoogle Scholar
  81. Kevelam SH, Rodenburg RJ, Wolf NI, Ferreira P, Lunsing RJ, Nijtmans LG, Mitchell A, Arroyo HA, Rating D, Vanderver A, van Berkel CG, Abbink TE, Heutink P, van der Knaap MS (2013) NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology 80(17):1577–1583. doi: 10.1212/WNL.0b013e31828f1914CrossRefPubMedPubMedCentralGoogle Scholar
  82. Kiley PJ, Beinert H (2003) The role of Fe-S proteins in sensing and regulation in bacteria. Curr Opin Microbiol 6(2):181–185CrossRefGoogle Scholar
  83. 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(14):3981–3989. doi: 10.1093/emboj/18.14.3981CrossRefPubMedPubMedCentralGoogle Scholar
  84. Kollberg G, Tulinius M, Melberg A, Darin N, Andersen O, Holmgren D, Oldfors A, Holme E (2009) Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain 132(8):2170–2179. doi: 10.1093/brain/awp152CrossRefPubMedGoogle Scholar
  85. Lange H, Kispal G, Lill R (1999) Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J Biol Chem 274(27):18989–18996CrossRefGoogle Scholar
  86. 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 U S A 97(3):1050–1055CrossRefGoogle Scholar
  87. Lange H, Lisowsky T, Gerber J, Muhlenhoff U, Kispal G, Lill R (2001) An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins. EMBO Rep 2(8):715–720. doi: 10.1093/embo-reports/kve161CrossRefPubMedPubMedCentralGoogle Scholar
  88. Langlois d’Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Precigoux G, Levi S, Arosio P (2004) Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. J Mol Biol 340(2):277–293. doi: 10.1016/j.jmb.2004.04.036CrossRefPubMedGoogle Scholar
  89. Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J (2001) A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem 276(27):24437–24440. doi: 10.1074/jbc.C100141200CrossRefPubMedGoogle Scholar
  90. Li J, Cowan JA (2015) Glutathione-coordinated [2Fe-2S] cluster: a viable physiological substrate for mitochondrial ABCB7 transport. Chem Commun (Camb) 51(12):2253–2255. doi: 10.1039/c4cc09175bCrossRefGoogle Scholar
  91. Li H, Outten CE (2012) Monothiol CGFS glutaredoxins and BolA-like proteins: [2Fe-2S] binding partners in iron homeostasis. Biochemistry 51(22):4377–4389. doi: 10.1021/bi300393zCrossRefPubMedPubMedCentralGoogle Scholar
  92. Li J, Kogan M, Knight SA, Pain D, Dancis A (1999) Yeast mitochondrial protein, Nfs1p, coordinately regulates iron-sulfur cluster proteins, cellular iron uptake, and iron distribution. J Biol Chem 274(46):33025–33034CrossRefGoogle Scholar
  93. Li J, Saxena S, Pain D, Dancis A (2001) Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria required for iron homeostasis. J Biol Chem 276(2):1503–1509. doi: 10.1074/jbc.M007198200CrossRefPubMedGoogle Scholar
  94. Lill R (2009) Function and biogenesis of iron-sulphur proteins. Nature 460(7257):831–838. doi: 10.1038/nature08301CrossRefPubMedGoogle Scholar
  95. Lill R, Kispal G (2000) Maturation of cellular Fe-S proteins: an essential function of mitochondria. Trends Biochem Sci 25(8):352–356CrossRefGoogle Scholar
  96. Lill R, Muhlenhoff U (2005) Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem Sci 30(3):133–141. doi: 10.1016/j.tibs.2005.01.006CrossRefPubMedGoogle Scholar
  97. Lill R, Muhlenhoff U (2006) Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms. Annu Rev Cell Dev Biol 22:457–486. doi: 10.1146/annurev.cellbio.22.010305.104538CrossRefPubMedGoogle Scholar
  98. Lill R, Muhlenhoff U (2008) Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem 77:669–700. doi: 10.1146/annurev.biochem.76.052705.162653CrossRefPubMedGoogle Scholar
  99. Lill R, Dutkiewicz R, Elsasser HP, Hausmann A, Netz DJ, Pierik AJ, Stehling O, Urzica E, Muhlenhoff U (2006) Mechanisms of iron-sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes. Biochim Biophys Acta 1763(7):652–667. doi: 10.1016/j.bbamcr.2006.05.011CrossRefPubMedGoogle Scholar
  100. Lill R, Hoffmann B, Molik S, Pierik AJ, Rietzschel N, Stehling O, Uzarska MA, Webert H, Wilbrecht C, Muhlenhoff U (2012) The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism. Biochim Biophys Acta 1823(9):1491–1508. doi: 10.1016/j.bbamcr.2012.05.009CrossRefPubMedGoogle Scholar
  101. Lim SC, Friemel M, Marum JE, Tucker EJ, Bruno DL, Riley LG, Christodoulou J, Kirk EP, Boneh A, DeGennaro CM, Springer M, Mootha VK, Rouault TA, Leimkuhler S, Thorburn DR, Compton AG (2013) Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes. Hum Mol Genet 22(22):4460–4473. doi: 10.1093/hmg/ddt295CrossRefPubMedPubMedCentralGoogle Scholar
  102. Liu G, Guo S, Anderson GJ, Camaschella C, Han B, Nie G (2014) Heterozygous missense mutations in the GLRX5 gene cause sideroblastic anemia in a Chinese patient. Blood 124(17):2750–2751. doi: 10.1182/blood-2014-08-598508CrossRefPubMedGoogle Scholar
  103. Lossos A, Stumpfig C, Stevanin G, Gaussen M, Zimmerman BE, Mundwiller E, Asulin M, Chamma L, Sheffer R, Misk A, Dotan S, Gomori JM, Ponger P, Brice A, Lerer I, Meiner V, Lill R (2015) Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology 84(7):659–667. doi: 10.1212/WNL.0000000000001270CrossRefPubMedGoogle Scholar
  104. Lu J, Bitoun JP, Tan G, Wang W, Min W, Ding H (2010) Iron-binding activity of human iron-sulfur cluster assembly protein hIscA1. Biochem J 428(1):125–131. doi: 10.1042/BJ20100122CrossRefPubMedPubMedCentralGoogle Scholar
  105. Maio N, Rouault TA (2015) Iron-sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery. Biochim Biophys Acta 1853(6):1493–1512. doi: 10.1016/j.bbamcr.2014.09.009CrossRefPubMedGoogle Scholar
  106. Maio N, Singh A, Uhrigshardt H, Saxena N, Tong WH, Rouault TA (2014) Cochaperone binding to LYR motifs confers specificity of iron sulfur cluster delivery. Cell Metab 19(3):445–457. doi: 10.1016/j.cmet.2014.01.015CrossRefPubMedGoogle Scholar
  107. Marelja Z, Stocklein W, Nimtz M, Leimkuhler S (2008) A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. J Biol Chem 283(37):25178–25185. doi: 10.1074/jbc.M804064200CrossRefPubMedGoogle Scholar
  108. Marelja Z, Mullick Chowdhury M, Dosche C, Hille C, Baumann O, Lohmannsroben HG, Leimkuhler S (2013) The L-cysteine desulfurase NFS1 is localized in the cytosol where it provides the sulfur for molybdenum cofactor biosynthesis in humans. PLoS One 8(4):e60869. doi: 10.1371/journal.pone.0060869CrossRefPubMedPubMedCentralGoogle Scholar
  109. Melber A, Na U, Vashisht A, Weiler BD, Lill R, Wohlschlegel JA, Winge DR (2016) Role of Nfu1 and Bol3 in iron-sulfur cluster transfer to mitochondrial clients. Elife 5. doi: 10.7554/eLife.15991
  110. Merchant S, Dreyfuss BW (1998) Posttranslational assembly of photosynthetic metalloproteins. Annu Rev Plant Physiol Plant Mol Biol 49:25–51. doi: 10.1146/annurev.arplant.49.1.25CrossRefPubMedGoogle Scholar
  111. Mesecke N, Terziyska N, Kozany C, Baumann F, Neupert W, Hell K, Herrmann JM (2005) A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell 121(7):1059–1069. doi: 10.1016/j.cell.2005.04.011CrossRefPubMedGoogle Scholar
  112. Meyer J (2008) Iron-sulfur protein folds, iron-sulfur chemistry, and evolution. J Biol Inorg Chem 13(2):157–170. doi: 10.1007/s00775-007-0318-7CrossRefPubMedGoogle Scholar
  113. Muhlenhoff U, Richhardt N, Gerber J, Lill R (2002a) Characterization of iron-sulfur protein assembly in isolated mitochondria. A requirement for ATP, NADH, and reduced iron. J Biol Chem 277(33):29810–29816. doi: 10.1074/jbc.M204675200CrossRefPubMedGoogle Scholar
  114. Muhlenhoff U, Richhardt N, Ristow M, Kispal G, Lill R (2002b) The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. Hum Mol Genet 11(17):2025–2036CrossRefGoogle Scholar
  115. 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(18):4815–4825. doi: 10.1093/emboj/cdg446CrossRefPubMedPubMedCentralGoogle Scholar
  116. 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(42):40612–40620. doi: 10.1074/jbc.M307847200CrossRefPubMedGoogle Scholar
  117. Muhlenhoff U, Richter N, Pines O, Pierik AJ, Lill R (2011) Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe-4S] proteins. J Biol Chem 286(48):41205–41216. doi: 10.1074/jbc.M111.296152CrossRefPubMedPubMedCentralGoogle Scholar
  118. Nair M, Adinolfi S, Pastore C, Kelly G, Temussi P, Pastore A (2004) Solution structure of the bacterial frataxin ortholog, CyaY: mapping the iron binding sites. Structure 12(11):2037–2048. doi: 10.1016/j.str.2004.08.012CrossRefPubMedGoogle Scholar
  119. Nakai Y, Nakai M, Lill R, Suzuki T, Hayashi H (2007) Thio modification of yeast cytosolic tRNA is an iron-sulfur protein-dependent pathway. Mol Cell Biol 27(8):2841–2847. doi: 10.1128/MCB.01321-06CrossRefPubMedPubMedCentralGoogle Scholar
  120. Navarro-Sastre A, Tort F, Stehling O, Uzarska MA, Arranz JA, Del Toro M, Labayru MT, Landa J, Font A, Garcia-Villoria J, Merinero B, Ugarte M, Gutierrez-Solana LG, Campistol J, Garcia-Cazorla A, Vaquerizo J, Riudor E, Briones P, Elpeleg O, Ribes A, Lill R (2011) A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins. Am J Hum Genet 89(5):656–667. doi: 10.1016/j.ajhg.2011.10.005CrossRefPubMedPubMedCentralGoogle Scholar
  121. Naylor DJ, Stines AP, Hoogenraad NJ, Hoj PB (1998) Evidence for the existence of distinct mammalian cytosolic, microsomal, and two mitochondrial GrpE-like proteins, the co-chaperones of specific Hsp70 members. J Biol Chem 273(33):21169–21177CrossRefGoogle Scholar
  122. Netz DJ, Pierik AJ, Stumpfig M, Muhlenhoff U, Lill R (2007) The Cfd1-Nbp35 complex acts as a scaffold for iron-sulfur protein assembly in the yeast cytosol. Nat Chem Biol 3(5):278–286. doi: 10.1038/nchembio872CrossRefPubMedGoogle Scholar
  123. Netz DJ, Stumpfig M, Dore C, Muhlenhoff U, Pierik AJ, Lill R (2010) Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis. Nat Chem Biol 6(10):758–765. doi: 10.1038/nchembio.432CrossRefPubMedGoogle Scholar
  124. Netz DJ, Pierik AJ, Stumpfig M, Bill E, Sharma AK, Pallesen LJ, Walden WE, Lill R (2012) A bridging [4Fe-4S] cluster and nucleotide binding are essential for function of the Cfd1-Nbp35 complex as a scaffold in iron-sulfur protein maturation. J Biol Chem 287(15):12365–12378. doi: 10.1074/jbc.M111.328914CrossRefPubMedPubMedCentralGoogle Scholar
  125. Nizon M, Boutron A, Boddaert N, Slama A, Delpech H, Sardet C, Brassier A, Habarou F, Delahodde A, Correia I, Ottolenghi C, de Lonlay P (2014) Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency. Mitochondrion 15:59–64. doi: 10.1016/j.mito.2014.01.003CrossRefPubMedGoogle Scholar
  126. Nordin A, Larsson E, Thornell LE, Holmberg M (2011) Tissue-specific splicing of ISCU results in a skeletal muscle phenotype in myopathy with lactic acidosis, while complete loss of ISCU results in early embryonic death in mice. Hum Genet 129(4):371–378. doi: 10.1007/s00439-010-0931-3CrossRefPubMedGoogle Scholar
  127. Nordin A, Larsson E, Holmberg M (2012) The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1. Hum Mutat 33(3):467–470. doi: 10.1002/humu.22002CrossRefPubMedGoogle Scholar
  128. Olsson A, Lind L, Thornell LE, Holmberg M (2008) Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum Mol Genet 17(11):1666–1672. doi: 10.1093/hmg/ddn057CrossRefPubMedGoogle Scholar
  129. Orme-Johnson WH (1973) Iron-sulfur proteins: structure and function. Annu Rev Biochem 42:159–204. doi: 10.1146/annurev.bi.42.070173.001111CrossRefPubMedGoogle Scholar
  130. Ozer HK, Dlouhy AC, Thornton JD, Hu J, Liu Y, Barycki JJ, Balk J, Outten CE (2015) Cytosolic Fe-S cluster protein maturation and iron regulation are independent of the mitochondrial Erv1/Mia40 import system. J Biol Chem 290(46):27829–27840. doi: 10.1074/jbc.M115.682179CrossRefPubMedPubMedCentralGoogle Scholar
  131. Pandey A, Golla R, Yoon H, Dancis A, Pain D (2012) Persulfide formation on mitochondrial cysteine desulfurase: enzyme activation by a eukaryote-specific interacting protein and Fe-S cluster synthesis. Biochem J 448(2):171–187. doi: 10.1042/BJ20120951CrossRefPubMedGoogle Scholar
  132. Pandey A, Gordon DM, Pain J, Stemmler TL, Dancis A, Pain D (2013) Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly. J Biol Chem 288(52):36773–36786. doi: 10.1074/jbc.M113.525857CrossRefPubMedPubMedCentralGoogle Scholar
  133. Pantopoulos K (2004) Iron metabolism and the IRE/IRP regulatory system: an update. Ann N Y Acad Sci 1012:1–13CrossRefGoogle Scholar
  134. Parent A, Elduque X, Cornu D, Belot L, Le Caer JP, Grandas A, Toledano MB, D’Autreaux B (2015) Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols. Nat Commun 6:5686. doi: 10.1038/ncomms6686CrossRefPubMedGoogle Scholar
  135. Paul VD, Lill R (2015) Biogenesis of cytosolic and nuclear iron-sulfur proteins and their role in genome stability. Biochim Biophys Acta 1853(6):1528–1539. doi: 10.1016/j.bbamcr.2014.12.018CrossRefPubMedGoogle Scholar
  136. Picciocchi A, Saguez C, Boussac A, Cassier-Chauvat C, Chauvat F (2007) CGFS-type monothiol glutaredoxins from the cyanobacterium Synechocystis PCC6803 and other evolutionary distant model organisms possess a glutathione-ligated [2Fe-2S] cluster. Biochemistry 46(51):15018–15026. doi: 10.1021/bi7013272CrossRefPubMedGoogle Scholar
  137. Pondarre C, Antiochos BB, Campagna DR, Clarke SL, Greer EL, Deck KM, McDonald A, Han AP, Medlock A, Kutok JL, Anderson SA, Eisenstein RS, Fleming MD (2006) The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum Mol Genet 15(6):953–964. doi: 10.1093/hmg/ddl012CrossRefPubMedGoogle Scholar
  138. Prischi F, Konarev PV, Iannuzzi C, Pastore C, Adinolfi S, Martin SR, Svergun DI, Pastore A (2010) Structural bases for the interaction of frataxin with the central components of iron-sulphur cluster assembly. Nat Commun 1:95. doi: 10.1038/ncomms1097CrossRefPubMedPubMedCentralGoogle Scholar
  139. Puccio H, Simon D, Cossee M, Criqui-Filipe P, Tiziano F, Melki J, Hindelang C, Matyas R, Rustin P, Koenig M (2001) Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet 27(2):181–186. doi: 10.1038/84818CrossRefPubMedGoogle Scholar
  140. Pukszta S, Schilke B, Dutkiewicz R, Kominek J, Moczulska K, Stepien B, Reitenga KG, Bujnicki JM, Williams B, Craig EA, Marszalek J (2010) Co-evolution-driven switch of J-protein specificity towards an Hsp70 partner. EMBO Rep 11(5):360–365. doi: 10.1038/embor.2010.29CrossRefPubMedPubMedCentralGoogle Scholar
  141. Raulfs EC, O’Carroll IP, Dos Santos PC, Unciuleac MC, Dean DR (2008) In vivo iron-sulfur cluster formation. Proc Natl Acad Sci U S A 105(25):8591–8596. doi: 10.1073/pnas.0803173105CrossRefPubMedPubMedCentralGoogle Scholar
  142. Rees DC (2002) Great metalloclusters in enzymology. Annu Rev Biochem 71:221–246. doi: 10.1146/annurev.biochem.71.110601.135406CrossRefPubMedGoogle Scholar
  143. Rees DC, Howard JB (2000) Nitrogenase: standing at the crossroads. Curr Opin Chem Biol 4(5):559–566CrossRefGoogle Scholar
  144. Rees DC, Howard JB (2003) The interface between the biological and inorganic worlds: iron-sulfur metalloclusters. Science 300(5621):929–931. doi: 10.1126/science.1083075CrossRefPubMedGoogle Scholar
  145. Ribbe MW, Hu Y, Hodgson KO, Hedman B (2014) Biosynthesis of nitrogenase metalloclusters. Chem Rev 114(8):4063–4080. doi: 10.1021/cr400463xCrossRefPubMedGoogle Scholar
  146. Rodriguez-Manzaneque MT, Ros J, Cabiscol E, Sorribas A, Herrero E (1999) Grx5 glutaredoxin plays a central role in protection against protein oxidative damage in Saccharomyces cerevisiae. Mol Cell Biol 19(12):8180–8190CrossRefGoogle Scholar
  147. Rodriguez-Manzaneque MT, Tamarit J, Belli G, Ros J, Herrero E (2002) Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol Biol Cell 13(4):1109–1121. doi: 10.1091/mbc.01-10-0517CrossRefPubMedPubMedCentralGoogle Scholar
  148. Rouault TA (2012) Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease. Dis Model Mech 5(2):155–164. doi: 10.1242/dmm.009019CrossRefPubMedPubMedCentralGoogle Scholar
  149. Rouault TA, Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6(4):345–351. doi: 10.1038/nrm1620CrossRefPubMedGoogle Scholar
  150. Rouault TA, Tong WH (2008) Iron-sulfur cluster biogenesis and human disease. Trends Genet 24(8):398–407. doi: 10.1016/j.tig.2008.05.008CrossRefPubMedPubMedCentralGoogle Scholar
  151. Royer-Bertrand B, Castillo-Taucher S, Moreno-Salinas R, Cho TJ, Chae JH, Choi M, Kim OH, Dikoglu E, Campos-Xavier B, Girardi E, Superti-Furga G, Bonafe L, Rivolta C, Unger S, Superti-Furga A (2015) Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia. Sci Rep 5:17154. doi: 10.1038/srep17154CrossRefPubMedPubMedCentralGoogle Scholar
  152. Saha PP, Kumar SK, Srivastava S, Sinha D, Pareek G, D’Silva P (2014) The presence of multiple cellular defects associated with a novel G50E iron-sulfur cluster scaffold protein (ISCU) mutation leads to development of mitochondrial myopathy. J Biol Chem 289(15):10359–10377. doi: 10.1074/jbc.M113.526665CrossRefPubMedPubMedCentralGoogle Scholar
  153. Saha PP, Srivastava S, Kumar SKP, Sinha D, D’Silva P (2015) Mapping key residues of ISD11 critical for NFS1-ISD11 subcomplex stability: implications in the development of mitochondrial disorder, COXPD19. J Biol Chem 290(43):25876–25890. doi: 10.1074/jbc.M115.678508CrossRefPubMedPubMedCentralGoogle Scholar
  154. 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(16):1660–1665. doi: 10.1016/j.cub.2006.06.069CrossRefPubMedGoogle Scholar
  155. Schmitz-Abe K, Ciesielski SJ, Schmidt PJ, Campagna DR, Rahimov F, Schilke BA, Cuijpers M, Rieneck K, Lausen B, Linenberger ML, Sendamarai AK, Guo C, Hofmann I, Newburger PE, Matthews D, Shimamura A, Snijders PJ, Towne MC, Niemeyer CM, Watson HG, Dziegiel MH, Heeney MM, May A, Bottomley SS, Swinkels DW, Markianos K, Craig EA, Fleming MD (2015) Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9. Blood 126(25):2734–2738. doi: 10.1182/blood-2015-09-659854CrossRefPubMedPubMedCentralGoogle Scholar
  156. Shakamuri P, Zhang B, Johnson MK (2012) Monothiol glutaredoxins function in storing and transporting [Fe2S2] clusters assembled on IscU scaffold proteins. J Am Chem Soc 134(37):15213–15216. doi: 10.1021/ja306061xCrossRefPubMedPubMedCentralGoogle Scholar
  157. Sheftel AD, Stehling O, Pierik AJ, Netz DJ, Kerscher S, Elsasser HP, Wittig I, Balk J, Brandt U, Lill R (2009) Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I. Mol Cell Biol 29(22):6059–6073. doi: 10.1128/MCB.00817-09CrossRefPubMedPubMedCentralGoogle Scholar
  158. Sheftel AD, Stehling O, Pierik AJ, Elsasser HP, Muhlenhoff 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 U S A 107(26):11775–11780. doi: 10.1073/pnas.1004250107CrossRefPubMedPubMedCentralGoogle Scholar
  159. Sheftel AD, Wilbrecht C, Stehling O, Niggemeyer B, Elsasser HP, Muhlenhoff U, Lill R (2012) The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation. Mol Biol Cell 23(7):1157–1166. doi: 10.1091/mbc.E11-09-0772CrossRefPubMedPubMedCentralGoogle Scholar
  160. 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(16):3014–3025. doi: 10.1093/hmg/ddp239CrossRefPubMedPubMedCentralGoogle Scholar
  161. Shi Y, Ghosh M, Kovtunovych G, Crooks DR, Rouault TA (2012) Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis. Biochim Biophys Acta 1823(2):484–492. doi: 10.1016/j.bbamcr.2011.11.002CrossRefPubMedGoogle Scholar
  162. Shimomura Y, Kamikubo H, Nishi Y, Masako T, Kataoka M, Kobayashi Y, Fukuyama K, Takahashi Y (2007) Characterization and crystallization of an IscU-type scaffold protein with bound [2Fe-2S] cluster from the hyperthermophile, aquifex aeolicus. J Biochem 142(5):577–586. doi: 10.1093/jb/mvm163CrossRefPubMedGoogle Scholar
  163. Shimomura Y, Wada K, Fukuyama K, Takahashi Y (2008) The asymmetric trimeric architecture of [2Fe-2S] IscU: implications for its scaffolding during iron-sulfur cluster biosynthesis. J Mol Biol 383(1):133–143. doi: 10.1016/j.jmb.2008.08.015CrossRefPubMedGoogle Scholar
  164. Sipos K, Lange H, Fekete Z, Ullmann P, Lill R, Kispal G (2002) Maturation of cytosolic iron-sulfur proteins requires glutathione. J Biol Chem 277(30):26944–26949. doi: 10.1074/jbc.M200677200CrossRefPubMedGoogle Scholar
  165. Smith AD, Agar JN, Johnson KA, Frazzon J, Amster IJ, Dean DR, Johnson MK (2001) Sulfur transfer from IscS to IscU: the first step in iron-sulfur cluster biosynthesis. J Am Chem Soc 123(44):11103–11104CrossRefGoogle Scholar
  166. Song D, Lee FS (2008) A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis. J Biol Chem 283(14):9231–9238. doi: 10.1074/jbc.M708077200CrossRefPubMedPubMedCentralGoogle Scholar
  167. Song D, Lee FS (2011) Mouse knock-out of IOP1 protein reveals its essential role in mammalian cytosolic iron-sulfur protein biogenesis. J Biol Chem 286(18):15797–15805. doi: 10.1074/jbc.M110.201731CrossRefPubMedPubMedCentralGoogle Scholar
  168. Song D, Tu Z, Lee FS (2009) Human ISCA1 interacts with IOP1/NARFL and functions in both cytosolic and mitochondrial iron-sulfur protein biogenesis. J Biol Chem 284(51):35297–35307. doi: 10.1074/jbc.M109.040014CrossRefPubMedPubMedCentralGoogle Scholar
  169. Spiegel R, Saada A, Halvardson J, Soiferman D, Shaag A, Edvardson S, Horovitz Y, Khayat M, Shalev SA, Feuk L, Elpeleg O (2014) Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy. Eur J Hum Genet 22(7):902–906. doi: 10.1038/ejhg.2013.269CrossRefPubMedGoogle Scholar
  170. Stehling O, Vashisht AA, Mascarenhas J, Jonsson ZO, Sharma T, Netz DJ, Pierik AJ, Wohlschlegel JA, Lill R (2012) MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science 337(6091):195–199. doi: 10.1126/science.1219723CrossRefPubMedPubMedCentralGoogle Scholar
  171. Stehling O, Mascarenhas J, Vashisht AA, Sheftel AD, Niggemeyer B, Rosser R, Pierik AJ, Wohlschlegel JA, Lill R (2013) Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins. Cell Metab 18(2):187–198. doi: 10.1016/j.cmet.2013.06.015CrossRefPubMedPubMedCentralGoogle Scholar
  172. Stehling O, Wilbrecht C, Lill R (2014) Mitochondrial iron-sulfur protein biogenesis and human disease. Biochimie 100:61–77. doi: 10.1016/j.biochi.2014.01.010CrossRefPubMedGoogle Scholar
  173. Tonduti D, Dorboz I, Imbard A, Slama A, Boutron A, Pichard S, Elmaleh M, Vallee L, Benoist JF, Ogier H, Boespflug-Tanguy O (2015) New spastic paraplegia phenotype associated to mutation of NFU1. Orphanet J Rare Dis 10:13. doi: 10.1186/s13023-015-0237-6CrossRefPubMedPubMedCentralGoogle Scholar
  174. Tong WH, Rouault T (2000) Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J 19(21):5692–5700. doi: 10.1093/emboj/19.21.5692CrossRefPubMedPubMedCentralGoogle Scholar
  175. Tong WH, Jameson GN, Huynh BH, Rouault TA (2003) Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster. Proc Natl Acad Sci U S A 100(17):9762–9767. doi: 10.1073/pnas.1732541100CrossRefPubMedPubMedCentralGoogle Scholar
  176. Tucker EJ, Mimaki M, Compton AG, McKenzie M, Ryan MT, Thorburn DR (2012) Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. Hum Mutat 33(2):411–418. doi: 10.1002/humu.21654CrossRefPubMedGoogle Scholar
  177. 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(19):3816–3834. doi: 10.1093/hmg/ddq301CrossRefPubMedPubMedCentralGoogle Scholar
  178. Unciuleac MC, Chandramouli K, Naik S, Mayer S, Huynh BH, Johnson MK, Dean DR (2007) In vitro activation of apo-aconitase using a [4Fe-4S] cluster-loaded form of the IscU [Fe-S] cluster scaffolding protein. Biochemistry 46(23):6812–6821. doi: 10.1021/bi6026665CrossRefPubMedGoogle Scholar
  179. Urbina HD, Silberg JJ, Hoff KG, Vickery LE (2001) Transfer of sulfur from IscS to IscU during Fe/S cluster assembly. J Biol Chem 276(48):44521–44526. doi: 10.1074/jbc.M106907200CrossRefPubMedGoogle Scholar
  180. Urzica E, Pierik AJ, Muhlenhoff U, Lill R (2009) Crucial role of conserved cysteine residues in the assembly of two iron-sulfur clusters on the CIA protein Nar1. Biochemistry 48(22):4946–4958. doi: 10.1021/bi900312xCrossRefPubMedGoogle Scholar
  181. Uzarska MA, Dutkiewicz R, Freibert SA, Lill R, Muhlenhoff U (2013) The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation. Mol Biol Cell 24(12):1830–1841. doi: 10.1091/mbc.E12-09-0644CrossRefPubMedPubMedCentralGoogle Scholar
  182. Van Vranken JG, Jeong MY, Wei P, Chen YC, Gygi SP, Winge DR, Rutter J (2016) The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. Elife 5. doi: 10.7554/eLife.17828
  183. Vernis L, Facca C, Delagoutte E, Soler N, Chanet R, Guiard B, Faye G, Baldacci G (2009) A newly identified essential complex, Dre2-Tah18, controls mitochondria integrity and cell death after oxidative stress in yeast. PLoS One 4(2):e4376. doi: 10.1371/journal.pone.0004376CrossRefPubMedPubMedCentralGoogle Scholar
  184. Wadhwa R, Ryu J, Ahn HM, Saxena N, Chaudhary A, Yun CO, Kaul SC (2015) Functional significance of point mutations in stress chaperone mortalin and their relevance to Parkinson disease. J Biol Chem 290(13):8447–8456. doi: 10.1074/jbc.M114.627463CrossRefPubMedPubMedCentralGoogle Scholar
  185. Wang Y, Langer NB, Shaw GC, Yang G, Li L, Kaplan J, Paw BH, Bloomer JR (2011) Abnormal mitoferrin-1 expression in patients with erythropoietic protoporphyria. Exp Hematol 39(7):784–794. doi: 10.1016/j.exphem.2011.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  186. Webert H, Freibert SA, Gallo A, Heidenreich T, Linne U, Amlacher S, Hurt E, Muhlenhoff U, Banci L, Lill R (2014) Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin. Nat Commun 5:5013. doi: 10.1038/ncomms6013CrossRefPubMedGoogle Scholar
  187. Westermann B, Prip-Buus C, Neupert W, Schwarz E (1995) The role of the GrpE homologue, Mge1p, in mediating protein import and protein folding in mitochondria. EMBO J 14(14):3452–3460PubMedPubMedCentralGoogle Scholar
  188. Wiedemann N, Urzica E, Guiard B, Muller H, Lohaus C, Meyer HE, Ryan MT, Meisinger C, Muhlenhoff U, Lill R, Pfanner N (2006) Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins. EMBO J 25(1):184–195. doi: 10.1038/sj.emboj.7600906CrossRefPubMedGoogle Scholar
  189. Willems P, Wanschers BF, Esseling J, Szklarczyk R, Kudla U, Duarte I, Forkink M, Nooteboom M, Swarts H, Gloerich J, Nijtmans L, Koopman W, Huynen MA (2013) BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion. Antioxid Redox Signal 18(2):129–138. doi: 10.1089/ars.2011.4253CrossRefPubMedPubMedCentralGoogle Scholar
  190. Wittung-Stafshede P (2002) Role of cofactors in protein folding. Acc Chem Res 35(4):201–208CrossRefGoogle Scholar
  191. Wohlgamuth-Benedum JM, Rubio MA, Paris Z, Long S, Poliak P, Lukes J, Alfonzo JD (2009) Thiolation controls cytoplasmic tRNA stability and acts as a negative determinant for tRNA editing in mitochondria. J Biol Chem 284(36):23947–23953. doi: 10.1074/jbc.M109.029421CrossRefPubMedPubMedCentralGoogle Scholar
  192. Wu G, Mansy SS, Wu Sp SP, Surerus KK, Foster MW, Cowan JA (2002) Characterization of an iron-sulfur cluster assembly protein (ISU1) from Schizosaccharomyces pombe. Biochemistry 41(15):5024–5032CrossRefGoogle Scholar
  193. Wydro MM, Balk J (2013) Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model. Dis Model Mech 6(5):1279–1284. doi: 10.1242/dmm.012682CrossRefPubMedPubMedCentralGoogle Scholar
  194. Yan R, Adinolfi S, Pastore A (2015) Ferredoxin, in conjunction with NADPH and ferredoxin-NADP reductase, transfers electrons to the IscS/IscU complex to promote iron-sulfur cluster assembly. Biochim Biophys Acta 1854(9):1113–1117. doi: 10.1016/j.bbapap.2015.02.002CrossRefPubMedPubMedCentralGoogle Scholar
  195. Ye H, Rouault TA (2010) Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 49(24):4945–4956. doi: 10.1021/bi1004798CrossRefPubMedPubMedCentralGoogle Scholar
  196. 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(20):6078–6084. doi: 10.1021/ja027967iCrossRefPubMedGoogle Scholar
  197. 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(20):19794–19807. doi: 10.1074/jbc.M500397200CrossRefPubMedGoogle Scholar
  198. Zheng L, White RH, Cash VL, Jack RF, Dean DR (1993) Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis. Proc Natl Acad Sci U S A 90(7):2754–2758CrossRefGoogle Scholar
  199. Zhou YB, Cao JB, Wan BB, Wang XR, Ding GH, Zhu H, Yang HM, Wang KS, Zhang X, Han ZG (2008) hBolA, novel non-classical secreted proteins, belonging to different BolA family with functional divergence. Mol Cell Biochem 317(1–2):61–68. doi: 10.1007/s11010-008-9809-2CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Prasenjit Prasad Saha
    • 1
  • Vinaya Vishwanathan
    • 1
  • Kondalarao Bankapalli
    • 1
  • Patrick D’Silva
    • 1
  1. 1.Department of BiochemistryIndian Institute of ScienceBengaluruIndia

Personalised recommendations