Publikationsserver der Universitätsbibliothek Marburg
Titel:Mechanistic characterization of the late steps of mitochondrial iron-sulfur cluster protein maturation.
Autor:Uzarska, Marta Agata
Weitere Beteiligte: Lill, Roland (Prof. Dr.)
Veröffentlicht:2013
URI:https://archiv.ub.uni-marburg.de/diss/z2013/0491
DOI: https://doi.org/10.17192/z2013.0491
URN: urn:nbn:de:hebis:04-z2013-04910
DDC:500 Naturwissenschaften
Titel (trans.):Mechanistische Charakterisierung der späten Schritte der mitochondrialen Eisen-Schwefel Protein Maturierung.
Publikationsdatum:2013-11-25
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Eisen, Mitochondrien, Saccharomyces cerevisiae, mitochondria,, Eisen, Iron-sulfur clusters

Summary:
Eisen-Schwefel (Fe/S) Cluster gehören zu den ältesten Co-Faktoren und sind unabdingbar für die Funktion vieler Proteine. Die Synthese von Fe/S Clustern und deren Insertion in Apoproteine sind komplexe biochemische Vorgänge. In Mitochondrien wird die Biogenese von Fe/S Proteinen durch die ISC Assemblierungsmaschinerie (Iron-Sulfur Cluster Assembly) in drei Stufen durchgeführt. Im ersten Schritt wird ein Fe/S Cluster de novo aus Eisenionen und Sulfid, das durch eine Cysteindesulfurase bereitgestellt wird, auf dem Gerüstprotein Isu1 assembliert. In einem zweiten Schritt wird der Isu1-gebundene Fe/S Cluster mittels eines spezifischen Chaperonsystems dissoziiert, um dann schließlich durch spezielle Reifungsfaktoren auf die verschiedenen Zielproteine übertragen zu werden. Obwohl bereits einige Faktoren identifiziert wurden, die am Transfer von Fe/S Clustern auf Zielproteine beteiligt sind, ist über deren Zusammenspiel und ihre jeweilige spezifische Funktion wenig bekannt. Diese Arbeit konzentriert sich auf die Rolle des Monothiol Glutaredoxin Grx5, der BolA-ähnlichen Proteine Aim1 und Yal044W sowie des Nfu1 in den späten Phasen der Fe/S Proteinbiogenese. Mutationen im humanen GLRX5 wurden mit mikrozytischer Anämie in Verbindung gebracht und eine Deletion im Zebrafisch ist embryonisch letal. In der Hefe S. cerevisiae ist Grx5 nicht essentiell, jedoch zeigen Zellen ohne Grx5 niedrige Enzymaktivitäten von Fe/S Proteinen, eine Akkumulation von mitochondrialem Eisen und oxidativen Stress. Es wurde bereits gezeigt, dass die Depletion von Grx5 eine Akkumulation von Fe/S Clustern auf Isu1 hervorruft, und diese nicht auf Zielproteine übertragen werden können. In dieser Arbeit konnte gezeigt werden, dass Grx5 einen Fe/S Cluster in vivo bindet, der für die Reifung aller zellulärer Fe/S Proteine benötigt wird, unabhängig vom Typ des gebundenen Fe/S Co-Faktors und deren subzellulärer Lokalisation. Grx5 und Isu1 interagieren gleichzeitig mit dem Hsp70 Chaperon Ssq1 an unterschiedlichen Bindungsstellen. Grx5 stimuliert dabei nicht die ATPase Aktivität von Ssq1 und bindet bevorzugt an die ADP-Form von Ssq1. Die räumliche Nähe von Isu1 und Grx5 am Chaperon erleichtert den schnellen Fe/S Cluster Transfer von Isu1 auf Grx5. Somit verbindet Grx5 den Prozess der de novo Fe/S Clusterbiosynthese auf Isu1 mit dem Transfer des fertigen Fe/S Clusters auf entsprechende Zielproteine. BolA-ähnliche Proteine sind mit den Monothiol Glutaredoxinen über bioinformatische und experimentelle Ansätze in Zusammenhang gebracht worden. Um die Funktion der mitochondrialen BolA-ähnlichen Proteine zu studieren, wurden Hefezellen untersucht, in denen die Gene für Aim1 und Yal044W deletiert wurden. Während die Rolle der Yal044W in der Fe/S Proteinbiogenese unklar blieb, zeigten aim1Δ Zellen eine 50%-ige Abnahme der Enzym-Aktivitäten der Succinatdehydrogenase und der Lipoat-abhängigen Enzyme Pyruvat- und α-Ketoglutarat-Dehydrogenase. Die Aktivitäten der letzteren Enzyme sind abhängig von der Lipoat-Synthase Lip5, einem Fe/S Protein. Aim1 scheint für die katalytische Aktivierung, aber nicht für die de novo Insertion von Fe/S Clustern in Lip5 benötigt zu werden. Der Phänotyp von aim1Δ Zellen in Hefe ist kompatibel mit dem humaner Zellen aus Patienten mit fataler infantiler Enzephalopathie und/oder pulmonaler Hypertonie. Diese Erkrankung wird u.a. durch Mutationen im humanen Aim1 Homolog BOLA3 verursacht. Offensichtlich ist die Rolle der Aim1 Proteine als spezialisierte ISC Überträger-Proteine, die bei der Reifung einer Unterklasse mitochondrialer [4Fe-4S]-Proteine benötigt werden, in Eukaryoten konserviert. Mutationen im humanen NFU1 wurden ebenfalls mit fataler infantiler Enzephalopathie und/ oder pulmonaler Hypertonie in Verbindung gebracht. NFU1 wird für die Reifung der Fe/S Cluster der Atmungskettenkomplexe I und II und der Lipoat-Synthase in humanen Zellen benötigt. Nfu1-ähnliche Proteine binden Fe/S Cluster in vitro, woraus geschlossen wurde, dass Nfu1 ein Gerüstprotein ist, dass parallel zu Isu1 arbeitet. In dieser Arbeit wurde gezeigt, dass die Deletion von NFU1 in Hefe eine bis zu 5-fache Abnahme der Aktivitäten der Succinat-dehydrogenase und Lipoat-abhängiger Enzyme hervorruft. Dies stimmt mit den Befunden an NFU1 Patientenzellen überein. Hefe Nfu1, das eine Patienten-analoge Mutation trägt (Gly194Cys), bindet einen Fe/S Cluster wesentlich stabiler als das Wildtyp-Protein, und erlaubte somit erstmals den Nachweis einer Fe/S Cluster Bindung auf Nfu1 in vivo. Die Fe/S Cluster Bindung auf Nfu1 war abhängig von der ISC Assemblierungsmaschinerie einschließlich Isu1, was ausschließt, dass Nfu1 ein zu Isu1 alternatives Gerüstprotein ist. Aufgrund der verminderten Labilität des gebundenen Fe/S Clusters in Nfu1-Gly194Cys konnte dieses die Defekte der nfu1∆-Zellen in Hefe nur unvollständig retten, womit ein Einblick in die Krankheitsentstehung in menschlichen Patienten gegeben wurde. Die vorliegende Arbeit trägt zu einem besseren Verständnis bei, wie Fe/S Cluster nach ihrer de novo Synthese auf dem Gerüstprotein Isu1 in den Mitochondrien weiter transferiert werden. Die hier gezeigte gleichzeitige Interaktion von Isu1 und Grx5 auf dem spezialisierten Hsp70 Chaperon Ssq1 ermöglicht einen effizienten Transfer der Fe/S Cluster von Isu1 zu Grx5, das wiederum als wichtiger ISC Faktor für die Reifung aller zellulärer Fe/S Proteine charakterisiert werden konnte. Weiterhin konnte eine unterstützende Funktion der Hefeproteine Nfu1 und Aim1 als spezialisierte Reifungsfaktoren nachgewiesen werden. Diese Erkenntnisse erlauben einen besseren Einblick in das mechanistische Zusammenspiel der späten Komponenten der mitochondrialen ISC Assemblierungsmaschinerie.

Bibliographie / References

  1. Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
  2. Iwema, T., Picciocchi, A., Traore, D.A., Ferrer, J.L., Chauvat, F., and Jacquamet, L. (2009). Structural basis for delivery of the intact [Fe2S2] cluster by monothiol glutaredoxin. Biochemistry 48, 6041-6043.
  3. Hoff, K.G., Culler, S.J., Nguyen, P.Q., McGuire, R.M., Silberg, J.J., and Smolke, C.D. (2009). In vivo fluorescent detection of Fe-S clusters coordinated by human GRX2. Chem Biol 16, 1299-1308.
  4. Chan, M.K., Kim, J., and Rees, D.C. (1993). The nitrogenase FeMo-cofactor and P-cluster pair: 2.2 A resolution structures. Science 260, 792-794.
  5. Camaschella, C., Campanella, A., De Falco, L., Boschetto, L., Merlini, R., Silvestri, L., Levi, S., and Iolascon, A. (2007). The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood 110, 1353-1358. References 148
  6. Hoff, K.G., Ta, D.T., Tapley, T.L., Silberg, J.J., and Vickery, L.E. (2002). Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU. J Biol Chem 277, 27353-27359.
  7. Berndt, C., Lillig, C.H., and Holmgren, A. (2008). Thioredoxins and glutaredoxins as facilitators of protein folding. Biochim Biophys Acta 1783, 641-650.
  8. Gelling, C., Dawes, I.W., Richhardt, N., Lill, R., and Muhlenhoff, U. (2008). Mitochondrial Iba57p is required for Fe/S cluster formation on aconitase and activation of radical SAM enzymes. Mol Cell Biol 28, 1851-1861.
  9. Bukau, B., and Horwich, A.L. (1998). The Hsp70 and Hsp60 chaperone machines. Cell 92, 351-366.
  10. Onder, O., Yoon, H., Naumann, B., Hippler, M., Dancis, A., and Daldal, F. (2006). Modifications of the lipoamide-containing mitochondrial subproteome in a yeast mutant defective in cysteine desulfurase.
  11. Voisine, C., Schilke, B., Ohlson, M., Beinert, H., Marszalek, J., and Craig, E.A. (2000). Role of the mitochondrial Hsp70s, Ssc1 and Ssq1, in the maturation of Yfh1. Mol Cell Biol 20, 3677-3684.
  12. Pierik, A.J., Netz, D.J., and Lill, R. (2009). Analysis of iron-sulfur protein maturation in eukaryotes. Nat Protoc 4, 753-766.
  13. Knieszner, H., Schilke, B., Dutkiewicz, R., D'Silva, P., Cheng, S., Ohlson, M., Craig, E.A., and 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.
  14. Kuhnke, G., Neumann, K., Muhlenhoff, U., and Lill, R. (2006). Stimulation of the ATPase activity of the yeast mitochondrial ABC transporter Atm1p by thiol compounds. Mol Membr Biol 23, 173-184.
  15. Muhlenhoff, U., Stadler, J.A., Richhardt, N., Seubert, A., Eickhorst, T., Schweyen, R.J., Lill, R., and Wiesenberger, G. (2003b). A specific role of the yeast mitochondrial carriers MRS3/4p in mitochondrial iron acquisition under iron-limiting conditions. J Biol Chem 278, 40612-40620. References 155
  16. Sheftel, A.D., Stehling, O., Pierik, A.J., Netz, D.J., Kerscher, S., Elsasser, H.P., Wittig, I., Balk, J., Brandt, U., and Lill, R. (2009). Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I. Mol Cell Biol 29, 6059-6073.
  17. Urzica, E., Pierik, A.J., Muhlenhoff, U., and Lill, R. (2009). Crucial role of conserved cysteine residues in the assembly of two iron-sulfur clusters on the CIA protein Nar1. Biochemistry 48, 4946-4958.
  18. Gerber, J., Neumann, K., Prohl, C., Muhlenhoff, U., and 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, 4848-4857.
  19. Tovar, J., Leon-Avila, G., Sanchez, L.B., Sutak, R., Tachezy, J., van der Giezen, M., Hernandez, M., Muller, M., and Lucocq, J.M. (2003). Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature 426, 172-176.
  20. Wienken, C.J., Baaske, P., Rothbauer, U., Braun, D., and Duhr, S. (2010). Protein-binding assays in biological liquids using microscale thermophoresis. Nat Commun 1, 100.
  21. Xu, X.M., and Moller, S.G. (1998). Iron-sulfur cluster biogenesis systems and their crosstalk. Chembiochem 15, 2355-2362.
  22. Mayer, M.P., and Bukau, B. (2005). Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62, 670-684.
  23. Beinert, H. (2000). Iron-sulfur proteins: ancient structures, still full of surprises. J Biol Inorg Chem 5, 2-15.
  24. Bennett, J., and Scott, K.J. (1971). Quantitative staining of fraction I protein in polyacrylamide gels using Coomassie brillant blue. Anal Biochem. 43, 173-182.
  25. Shethna, Y.I., Dervarta, D.V., and Beinert, H. (1968). Non Heme (Iron-Sulfur) Proteins of Azotobacter Vinelandii. Biochem Biophys Res Commun 31, 862-868.
  26. Malkin, R., and Rabinowitz, J.C. (1966). The reconstitution of clostridial ferredoxin. Biochem Biophys Res Commun 23, 822-827.
  27. Dervarti, D.V., Ormejohn, W.H., Hansen, R.E., Beinert, H., Tsai, R.L., Tsibris, J.C.M., Bartholo, R.C., and Gunsalus, I.C. (1967). Identification of sulfur as component of the EPR signal at g equals 1.94 by isotopic substitution. Biochem Biophys Res Commun 26, 569-576.
  28. Raguzzi, F., Lesuisse, E., and Crichton, R.R. (1988). Iron storage in Saccharomyces cerevisiae. FEBS Lett 231, 253-258.
  29. Ciesielski, S.J., Schilke, B.A., Osipiuk, J., Bigelow, L., Mulligan, R., Majewska, J., Joachimiak, A., Marszalek, J., Craig, E.A., and Dutkiewicz, R. (2012). Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution. J Mol Biol 417, 1-12.
  30. Thiol redox proteomics identifies differential targets of cytosolic and mitochondrial glutaredoxin-2 isoforms in Saccharomyces cerevisiae. Reversible S-glutathionylation of DHBP synthase (RIB3). J. Proteomics 74, 2487-2497.
  31. Barras, F., Loiseau, L., and Py, B. (2005). How Escherichia coli and Saccharomyces cerevisiae build Fe/S proteins. Adv Microb Physiol 50, 41-101.
  32. Funk, M., Niedenthal, R., Mumberg, D., Brinkmann, K., Ronicke, V., and Henkel, T. (2002). Vector systems for heterologous expression of proteins in Saccharomyces cerevisiae. Methods Enzymol 350, 248-257.
  33. Jakubowski, W., and Bartosz, G. (1997). Estimation of oxidative stress in Saccharomyces cerevisae with fluorescent probes. Int J Biochem Cell Biol 29, 1297-1301.
  34. Frazzon, J., and Dean, D.R. (2003). Formation of iron-sulfur clusters in bacteria: an emerging field in bioinorganic chemistry. Curr Opin Chem Biol 7, 166-173.
  35. Tsai, C.L., and Barondeau, D.P. (2010). Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex. Biochemistry 49, 9132-9139.
  36. Formation and Properties of [4Fe-4S] Clusters on the IscU Scaffold Protein. Biochemistry 46, 6804-6811.
  37. Miao, R., Martinho, M., Morales, J.G., Kim, H., Ellis, E.A., Lill, R., Hendrich, M.P., Munck, E., and Lindahl, P.A. (2008). EPR and Mossbauer spectroscopy of intact mitochondria isolated from Yah1p-depleted Saccharomyces cerevisiae. Biochemistry 47, 9888-9899.
  38. Markiewicz, Z., Broome-Smith, J.K., Schwarz, U., and Spratt, B.G. (1982). Spherical E. coli due to elevated levels of D-alanine carboxypeptidase. Nature 297, 702-704.
  39. Schindelin, H., Kisker, C., Schlessman, J.L., Howard, J.B., and Rees, D.C. (1997). Structure of ADP x AIF4(-)- stabilized nitrogenase complex and its implications for signal transduction. Nature 387, 370-376.
  40. Wingert, R.A., Galloway, J.L., Barut, B., Foott, H., Fraenkel, P., Axe, J.L., Weber, G.J., Dooley, K., Davidson, A.J., Schmid, B., Paw, B.H., Shaw, G.C., Kingsley, P., Palis, J., Schubert, H., Chen, O., Kaplan, J., and Zon, L.I. (2005). Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436, 1035-1039.
  41. Py, B., and Barras, F. (2010). Building Fe-S proteins: bacterial strategies. Nat Rev Microbiol 8, 436-446.
  42. Schlecht, R., Erbse, A.H., Bukau, B., and Mayer, M.P. (2011). Mechanics of Hsp70 chaperones enables differential interaction with client proteins. Nat Struct Mol Biol 18, 345-351.
  43. Qi, W., and Cowan, J.A. (2011). Mechanism of glutaredoxin-ISU [2Fe-2S] cluster exchange. Chem Commun (Camb) 47, 4989-4991.
  44. Johansson, C., Roos, A.K., Montano, S.J., Sengupta, R., Filippakopoulos, P., Guo, K., von Delft, F., Holmgren, A., Oppermann, U., and Kavanagh, K.L. (2011). The crystal structure of human GLRX5: iron- sulfur cluster co-ordination, tetrameric assembly and monomer activity. Biochem J 433, 303-311.
  45. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F., and Marquet, A. (2005). Biotin synthase mechanism: an overview. Biochem Soc Trans 33, 820-823.
  46. Kosman, D.J. (2003). Molecular mechanisms of iron uptake in fungi. Mol Microbiol 47, 1185-1197.
  47. Urbanowski, J.L., and Piper, R.C. (1999). The iron transporter Fth1p forms a complex with the Fet5 iron oxidase and resides on the vacuolar membrane. J Biol Chem 274, 38061-38070.
  48. Shenton, D., Perrone, G., Quinn, K.A., Dawes, I.W., and Grant, C.M. (2002). Regulation of protein S- thiolation by glutaredoxin 5 in the yeast Saccharomyces cerevisiae. J Biol Chem 277, 16853-16859.
  49. Dutkiewicz, R., Schilke, B., Cheng, S., Knieszner, H., Craig, E.A., and 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.
  50. Chen, O.S., Crisp, R.J., Valachovic, M., Bard, M., Winge, D.R., and Kaplan, J. (2004). Transcription of the yeast iron regulon does not respond directly to iron but rather to iron-sulfur cluster biosynthesis. J Biol Chem 279, 29513-29518.
  51. Porras, P., Padilla, C.A., Krayl, M., Voos, W., and Barcena, J.A. (2006). One single in-frame AUG codon is responsible for a diversity of subcellular localizations of glutaredoxin 2 in Saccharomyces cerevisiae. J Biol Chem 281, 16551-16562.
  52. Andrew, A.J., Dutkiewicz, R., Knieszner, H., Craig, E.A., and Marszalek, J. (2006). Characterization of the interaction between the J-protein Jac1p and the scaffold for Fe-S cluster biogenesis, Isu1p. J Biol Chem 281, 14580-14587.
  53. Johansson, C., Kavanagh, K.L., Gileadi, O., and Oppermann, U. (2007). Reversible sequestration of active site cysteines in a 2Fe-2S-bridged dimer provides a mechanism for glutaredoxin 2 regulation in human mitochondria. J Biol Chem 282, 3077-3082.
  54. Kaut, A., Lange, H., Diekert, K., Kispal, G., and Lill, R. (2000). Isa1p is a component of the mitochondrial machinery for maturation of cellular iron-sulfur proteins and requires conserved cysteine residues for function. J Biol Chem 275, 15955-15961.
  55. Vickery, L.E., and Cupp-Vickery, J.R. (2007). Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur protein maturation. Crit Rev Biochem Mol Biol 42, 95-111.
  56. Bhan, A., Galas, D.J., and Dewey, T.G. (2002). A duplication growth model of gene expression networks. Bioinformatics 18, 1486-1493.
  57. Campuzano, V., Montermini, L., Lutz, Y., Cova, L., Hindelang, C., Jiralerspong, S., Trottier, Y., Kish, S.J., Faucheux, B., Trouillas, P., Authier, F.J., Durr, A., Mandel, J.L., Vescovi, A., Pandolfo, M., and Koenig, M. (1997). Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 6, 1771-1780.
  58. Outten, F.W., Djaman, O., and Storz, G. (2004). A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli. Mol Microbiol 52, 861-872.
  59. Touraine, B., Boutin, J.P., Marion-Poll, A., Briat, J.F., Peltier, G., and Lobreaux, S. (2004). Nfu2: a scaffold protein required for [4Fe-4S] and ferredoxin iron-sulphur cluster assembly in Arabidopsis chloroplasts. Plant J 40, 101-111.
  60. Stankiewicz, M., Nikolay, R., Rybin, V., and Mayer, M.P. (2011). CHIP participates in protein triage decisions by preferentially ubiquitinating Hsp70-bound substrates. Febs J 277, 3353-3367.
  61. The ISC proteins Isa1 and Isa2 are required for the function but not for the de novo synthesis of the Fe/S clusters of biotin synthase in Saccharomyces cerevisiae. Eukaryot Cell 6, 495-504.
  62. Pujol-Carrion, N., Belli, G., Herrero, E., Nogues, A., and de la Torre-Ruiz, M.A. (2006). Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae. J Cell Sci 119, 4554-4564. References 156
  63. Lill, R., Diekert, K., Kaut, A., Lange, H., Pelzer, W., Prohl, C., and Kispal, G. (1999). The essential role of mitochondria in the biogenesis of cellular iron-sulfur proteins. Biol Chem 380, 1157-1166.
  64. Pukszta, S., Schilke, B., Dutkiewicz, R., Kominek, J., Moczulska, K., Stepien, B., Reitenga, K.G., Bujnicki, J.M., Williams, B., Craig, E.A., and Marszalek, J. (2010). Co-evolution-driven switch of J-protein specificity towards an Hsp70 partner. EMBO Rep 11, 360-365.
  65. Shiflett, A.M., and Johnson, P.J. (2010). Mitochondrion-related organelles in eukaryotic protists. Annu. Rev. Microbiol. 64, 409-429.
  66. Pierrel, F., Hamelin, O., Douki, T., Kieffer-Jaquinod, S., Muhlenhoff, U., Ozeir, M., Lill, R., and Fontecave, M. (2010). Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis. Chem Biol 17, 449-459.
  67. Identification and expression of uvi31+, a UV-inducible gene from Schizosaccharomyces pombe. Environ Mol Mutagen 30, 72-81.
  68. Rodriguez-Manzaneque, M.T., Tamarit, J., Belli, G., Ros, J., and Herrero, E. (2002). Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol Biol Cell 13, 1109-1121.
  69. Rodriguez-Manzaneque, M.T., Ros, J., Cabiscol, E., Sorribas, A., and Herrero, E. (1999). Grx5 glutaredoxin plays a central role in protection against protein oxidative damage in Saccharomyces cerevisiae. Mol Cell Biol 19, 8180-8190.
  70. Herrero, E., and de la Torre-Ruiz, M.A. (2007). Monothiol glutaredoxins: a common domain for multiple functions. Cell Mol Life Sci 64, 1518-1530.
  71. Tamarit, J., Belli, G., Cabiscol, E., Herrero, E., and Ros, J. (2003). Biochemical characterization of yeast mitochondrial Grx5 monothiol glutaredoxin. J Biol Chem 278, 25745-25751.
  72. Molina, M.M., Belli, G., de la Torre, M.A., Rodriguez-Manzaneque, M.T., and Herrero, E. (2004). Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as mitochondrial glutaredoxins. J Biol Chem 279, 51923-51930.
  73. Belli, G., Polaina, J., Tamarit, J., De La Torre, M.A., Rodriguez-Manzaneque, M.T., Ros, J., and Herrero, E. (2002). Structure-function analysis of yeast Grx5 monothiol glutaredoxin defines essential amino acids for the function of the protein. J Biol Chem 277, 37590-37596.
  74. Muhlenhoff, U., Molik, S., Godoy, J.R., Uzarska, M.A., Richter, N., Seubert, A., Zhang, Y., Stubbe, J., Pierrel, F., Herrero, E., Lillig, C.H., and Lill, R. (2010). Cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron-sulfur cluster. Cell Metab 12, 373-385.
  75. Molina-Navarro, M.M., Casas, C., Piedrafita, L., Belli, G., and Herrero, E. (2006). Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria. FEBS Lett 580, 2273-2280. References 154
  76. Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332.
  77. Srinivasan, V., Netz, D.J., Webert, H., Mascarenhas, J., Pierik, A.J., Michel, H., and Lill, R. (2007). Structure of the yeast WD40 domain protein Cia1, a component acting late in iron-sulfur protein biogenesis. Structure 15, 1246-1257.
  78. Beinert, H.S., R. H. . (1960). Studies on Succinic and DPNH Dehydrogenase preparations by Paramagnetic Resonance (EPR) Spectroscopy. Biochem Biophys Res Commun 3, 41-46.
  79. Huynen, M.A., Spronk, C.A., Gabaldon, T., and Snel, B. (2005). Combining data from genomes, Y2H and 3D structure indicates that BolA is a reductase interacting with a glutaredoxin. FEBS Lett 579, 591-596.
  80. Bonomi, F., Iametti, S., Morleo, A., Ta, D., and Vickery, L.E. (2011). Facilitated transfer of IscU-[2Fe2S] clusters by chaperone-mediated ligand exchange. Biochemistry 50, 9641-9650.
  81. Takahashi, Y., and 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 (Tokyo) 126, 917-926.
  82. Goldberg, A.V., Molik, S., Tsaousis, A.D., Neumann, K., Kuhnke, G., Delbac, F., Vivares, C.P., Hirt, R.P., Lill, R., and Embley, T.M. (2008). Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature 452, 624-628.
  83. Gangon, P. (1998). An Enigma Unmasked: How Hydroxtapatite Works and How to Make it Work For You.
  84. Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248-254.
  85. Zheng, L., Cash, V.L., Flint, D.H., and Dean, D.R. (1998). Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J Biol Chem 273, 13264-13272.
  86. Li, L., Chen, O.S., McVey Ward, D., and Kaplan, J. (2001b). CCC1 is a transporter that mediates vacuolar iron storage in yeast. J Biol Chem 276, 29515-29519.
  87. Hausmann, A., Samans, B., Lill, R., and Muhlenhoff, U. (2008). Cellular and Mitochondrial Remodeling upon Defects in Iron-Sulfur Protein Biogenesis. J Biol Chem 283, 8318-8330.
  88. Picciocchi, A., Saguez, C., Boussac, A., Cassier-Chauvat, C., and 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, 15018-15026.
  89. Chaperonin-facilitated refolding of ribulosebisphosphate carboxylase and ATP hydrolysis by chaperonin 60 (groEL) are K+ dependent. Biochemistry 29, 5665-5671.
  90. Sun, F., Huo, X., Zhai, Y., Wang, A., Xu, J., Su, D., Bartlam, M., and Rao, Z. (2005). Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121, 1043-1057.
  91. Kyhse-Andersen, J. (1984). Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods. 10, 203- 209.
  92. Muhlenhoff, U., Balk, J., Richhardt, N., Kaiser, J.T., Sipos, K., Kispal, G., and Lill, R. (2004). Functional characterization of the eukaryotic cysteine desulfurase Nfs1p from Saccharomyces cerevisiae. J Biol Chem 279, 36906-36915.
  93. Lill, R. (2009). Function and biogenesis of iron-sulphur proteins. Nature 460, 831-838.
  94. Lillig, C.H., Berndt, C., and Holmgren, A. (2008). Glutaredoxin systems. Biochim Biophys Acta 1780, 1304- 1317.
  95. Amutha, B., Gordon, D.M., Gu, Y., Lyver, E.R., Dancis, A., and Pain, D. (2008). GTP is required for iron- sulfur cluster biogenesis in mitochondria. J Biol Chem 283, 1362-1371.
  96. Bekri, S., Kispal, G., Lange, H., Fitzsimons, E., Tolmie, J., Lill, R., and Bishop, D.F. (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, 3256-3264. References 147
  97. Gladyshev, V.N., Liu, A., Novoselov, S.V., Krysan, K., Sun, Q.A., Kryukov, V.M., Kryukov, G.V., and Lou, M.F. (2001). Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2. J Biol Chem 276, 30374-30380.
  98. Shethna, Y.I.B., H., Hansen, R. E.; Wilson, P. W. (1964). Identification by Isotopic Substitution of EPR Signal at G equals 1.94 in Non-Heme Iron Protein from Azotobacter. Proc Natl Acad Sci U S A 52, 1263- 1271. References 158
  99. Aldea, M., Garrido, T., Hernandez-Chico, C., Vicente, M., and Kushner, S.R. (1989). Induction of a growth- phase-dependent promoter triggers transcription of bolA, an Escherichia coli morphogene. Embo J 8, 3923-3931.
  100. Wu, S.P., and Cowan, J.A. (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. References 160
  101. Blaiseau, P.L., Seguin, A., Camadro, J.M., and Lesuisse, E. (2011). Iron Uptake in Yeasts. In: Iron Uptake and Homeostasis in Microorganisms, eds. P. Cornelis and S.C. Andrews, Norfolk, UK: Caister Academic Press, 265-284.
  102. Sipos, K., Lange, H., Fekete, Z., Ullmann, P., Lill, R., and Kispal, G. (2002). Maturation of cytosolic iron- sulfur proteins requires glutathione. J Biol Chem 277, 26944-26949.
  103. Mitochondrial fatty acid synthesis and respiration. Biochim Biophys Acta 1797, 1195-1202.
  104. Gari, K., Leon Ortiz, A.M., Borel, V., Flynn, H., Skehel, J.M., and Boulton, S.J. (2012). MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science 337, 243-245.
  105. Sambrook, J., and Russel, D.W. (2001). Molecular Cloning -A laboratory manual, 3rd edition. CSH Laboratory Press: ColdSpring Harbour, USA.
  106. Jerabek-Willemsen, M., Wienken, C.J., Braun, D., Baaske, P., and Duhr, S. (2011). Molecular interaction studies using microscale thermophoresis. Assay Drug Dev Technol 9, 342-353.
  107. Kim, K.D., Chung, W.H., Kim, H.J., Lee, K.C., and Roe, J.H. (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.
  108. Yoon, H., Golla, R., Lesuisse, E., Pain, J., Donald, J.E., Lyver, E.R., Pain, D., and Dancis, A. (2012). Mutation in the Fe-S scaffold protein Isu bypasses frataxin deletion. Biochem J 441, 473-480.
  109. Olsson, A., Lind, L., Thornell, L.E., and 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, 1666-1672.
  110. Xia, T.H., Bushweller, J.H., Sodano, P., Billeter, M., Bjornberg, O., Holmgren, A., and Wuthrich, K. (1992). NMR structure of oxidized Escherichia coli glutaredoxin: comparison with reduced E. coli glutaredoxin and functionally related proteins. Protein science : a publication of the Protein Society 1, 310-321.
  111. Vergara, S.V., and Thiele, D.J. (2008). Post-transcriptional regulation of gene expression in response to iron deficiency: co-ordinated metabolic reprogramming by yeast mRNA-binding proteins. Biochem Soc Trans 36, 1088-1090.
  112. D'Silva, P., Liu, Q., Walter, W., and Craig, E.A. (2004). Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nat Struct Mol Biol 11, 1084-1091.
  113. Silberg, J.J., Tapley, T.L., Hoff, K.G., and Vickery, L.E. (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.
  114. Djaman, O., Outten, F.W., and Imlay, J.A. (2004). Repair of oxidized iron-sulfur clusters in Escherichia coli. J Biol Chem 279, 44590-44599.
  115. Ojeda, L., Keller, G., Muhlenhoff, U., Rutherford, J.C., Lill, R., and Winge, D.R. (2006). Role of glutaredoxin-3 and glutaredoxin-4 in the iron regulation of the Aft1 transcriptional activator in Saccharomyces cerevisiae. J Biol Chem 281, 17661-17669.
  116. Garland, S.A., Hoff, K., Vickery, L.E., and Culotta, V.C. (1999). Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J Mol Biol 294, 897-907.
  117. Haas, H., Eisendle, M., and Turgeon, B.G. (2008). Siderophores in fungal physiology and virulence. Annu Rev Phytopathol 46, 149-187.
  118. Dutkiewicz, R., Schilke, B., Knieszner, H., Walter, W., Craig, E.A., and 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. References 149
  119. Bushweller, J.H., Aslund, F., Wuthrich, K., and Holmgren, A. (1992). Structural and functional characterization of the mutant Escherichia coli glutaredoxin (C14----S) and its mixed disulfide with glutathione. Biochemistry 31, 9288-9293.
  120. Wallace, M.A., Liou, L.L., Martins, J., Clement, M.H., Bailey, S., Longo, V.D., Valentine, J.S., and Gralla, E.B. (2004). Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis. Cross- compartment protection by CuZn-superoxide dismutase. J Biol Chem 279, 32055-32062.
  121. Balk, J., Aguilar Netz, D.J., Tepper, K., Pierik, A.J., and Lill, R. (2005). The essential WD40 protein Cia1 is involved in a late step of cytosolic and nuclear iron-sulfur protein assembly. Mol Cell Biol 25, 10833- 10841.
  122. Kakhlon, O., and Cabantchik, Z.I. (2002). The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic Biol Med 33, 1037-1046.
  123. Lill, R., Hoffmann, B., Molik, S., Pierik, A.J., Rietzschel, N., Stehling, O., Uzarska, M.A., Webert, H., Wilbrecht, C., and Muhlenhoff, U. (2012). The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism. Biochim Biophys Acta 1823, 1491-1508.
  124. Liu, X.F., Elashvili, I., Gralla, E.B., Valentine, J.S., Lapinskas, P., and Culotta, V.C. (1992). Yeast lacking superoxide dismutase. Isolation of genetic suppressors. J Biol Chem 267, 18298-18302.
  125. Haack, T.B., Rolinski, B., Haberberger, B., Zimmermann, F., Schum, J., Strecker, V., Graf, E., Athing, U., Hoppen, T., Wittig, I., Sperl, W., Freisinger, P., Mayr, J.A., Strom, T.M., Meitinger, T., and Prokisch, H. (2013). Homozygous missense mutation in BOLA3 causes multiple mitochondrial dysfunctions syndrome in two siblings. J Inherit Metab Dis 36, 55-62. References 150
  126. Shaw, G.C., Cope, J.J., Li, L., Corson, K., Hersey, C., Ackermann, G.E., Gwynn, B., Lambert, A.J., Wingert, R.A., Traver, D., Trede, N.S., Barut, B.A., Zhou, Y., Minet, E., Donovan, A., Brownlie, A., Balzan, R., Weiss, M.J., Peters, L.L., Kaplan, J., Zon, L.I., and Paw, B.H. (2006). Mitoferrin is essential for erythroid iron assimilation. Nature 440, 96-100.
  127. Birnboim, H.C., and Doly, J. (1979). A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic acids research 7, 1513-1523.
  128. Lill, R., and Muhlenhoff, U. (2006). Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms. Annu Rev Cell Dev Biol 22, 457-486. References 153
  129. Muhlenhoff, U., Gerber, J., Richhardt, N., and Lill, R. (2003a). Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. Embo J 22, 4815-4825.
  130. Kispal, G., Sipos, K., Lange, H., Fekete, Z., Bedekovics, T., Janaky, T., Bassler, J., Aguilar Netz, D.J., Balk, J., Rotte, C., and Lill, R. (2005). Biogenesis of cytosolic ribosomes requires the essential iron-sulphur protein Rli1p and mitochondria. Embo J 24, 589-598.
  131. Hoffmann, B., Uzarska, M.A., Berndt, C., Godoy, J.R., Haunhorst, P., Lillig, C.H., Lill, R., and Muhlenhoff, U. (2011). The multidomain thioredoxin-monothiol glutaredoxins represent a distinct functional group. Antioxid Redox Signal 15, 19-30.
  132. Gu, M., and Imlay, J.A. (2011). The SoxRS response of Escherichia coli is directly activated by redox- cycling drugs rather than by superoxide. Mol Microbiol 79, 1136-1150.
  133. Rouhier, N. (2010). Plant glutaredoxins: pivotal players in redox biology and iron-sulphur centre assembly. New Phytol 186, 365-372.
  134. In Vitro Activation of Apo-Aconitase Using a [4Fe-4S] Cluster-Loaded Form of the IscU [Fe-S] Cluster Scaffolding Protein. Biochemistry 46, 6812-6821. References 159
  135. Bonomi, F., Iametti, S., Morleo, A., Ta, D., and Vickery, L.E. (2008). Studies on the mechanism of catalysis of iron-sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry 47, 12795- 12801.
  136. Garg, R.P., Vargo, C.J., Cui, X., and Kurtz, D.M., Jr. (1996). A [2Fe-2S] protein encoded by an open reading frame upstream of the Escherichia coli bacterioferritin gene. Biochemistry 35, 6297-6301.
  137. van der Giezen, M., Tovar, J., and Clark, C.G. (2005). Mitochondrion-derived organelles in protists and fungi. Int Rev Cytol 244, 175-225.
  138. Rouhier, N., Lemaire, S.D., and Jacquot, J.P. (2008). The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation. Annu Rev Plant Biol 59, 143-166.
  139. Lill, R., and Muhlenhoff, U. (2008). Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem 77, 669-700.
  140. Li, J., Saxena, S., Pain, D., and Dancis, A. (2001a). Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria required for iron homeostasis. J Biol Chem 276, 1503-1509.
  141. Lundberg, M., Johansson, C., Chandra, J., Enoksson, M., Jacobsson, G., Ljung, J., Johansson, M., and Holmgren, A. (2001). Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. J Biol Chem 276, 26269-26275.
  142. Barros, M.H., Nobrega, F.G., and Tzagoloff, A. (2002). Mitochondrial ferredoxin is required for heme A synthesis in Saccharomyces cerevisiae. J Biol Chem 277, 9997-10002.
  143. Yamaguchi-Iwai, Y., Ueta, R., Fukunaka, A., and Sasaki, R. (2002). Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae. J Biol Chem 277, 18914-18918.
  144. Hoff, K.G., Cupp-Vickery, J.R., and Vickery, L.E. (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.
  145. Rutherford, J.C., Ojeda, L., Balk, J., Muhlenhoff, U., Lill, R., and Winge, D.R. (2005). Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial but not cytosolic iron- sulfur protein biogenesis. J Biol Chem 280, 10135-10140.
  146. Chacinska, A., Koehler, C.M., Milenkovic, D., Lithgow, T., and Pfanner, N. (2009). Importing mitochondrial proteins: machineries and mechanisms. Cell 138, 628-644.
  147. Characterization of human glutaredoxin 2 as iron-sulfur protein: a possible role as redox sensor. Proc Natl Acad Sci U S A 102, 8168-8173.
  148. Kispal, G., Csere, P., Prohl, C., and Lill, R. (1999). The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. Embo J 18, 3981-3989. References 152
  149. Pedrajas, J.R., Porras, P., Martinez-Galisteo, E., Padilla, C.A., Miranda-Vizuete, A., and Barcena, J.A. (2002). Two isoforms of Saccharomyces cerevisiae glutaredoxin 2 are expressed in vivo and localize to different subcellular compartments. Biochem J. 364, 617-623.
  150. Leon, S., Touraine, B., Ribot, C., Briat, J.F., and Lobreaux, S. (2003). Iron-sulphur cluster assembly in plants: distinct NFU proteins in mitochondria and plastids from Arabidopsis thaliana. Biochem J 371, 823- 830.
  151. Yi, X., and Maeda, N. (2005). Endogenous production of lipoic acid is essential for mouse development.
  152. Gerber, J., Muhlenhoff, U., and Lill, R. (2003). An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep 4, 906-911.
  153. Adam, A.C., Bornhovd, C., Prokisch, H., Neupert, W., and Hell, K. (2006). The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria. Embo J 25, 174-183.
  154. Wiedemann, N., Urzica, E., Guiard, B., Muller, H., Lohaus, C., Meyer, H.E., Ryan, M.T., Meisinger, C., Muhlenhoff, U., Lill, R., and Pfanner, N. (2006). Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins. Embo J 25, 184-195.
  155. Yang, M., Cobine, P.A., Molik, S., Naranuntarat, A., Lill, R., Winge, D.R., and Culotta, V.C. (2006). The effects of mitochondrial iron homeostasis on cofactor specificity of superoxide dismutase 2. Embo J 25, 1775-1783.
  156. Lange, H., Kaut, A., Kispal, G., and Lill, R. (2000). A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins. Proc Natl Acad Sci U S A 97, 1050-1055.
  157. Ito, T., Tashiro, K., Muta, S., Ozawa, R., Chiba, T., Nishizawa, M., Yamamoto, K., Kuhara, S., and Sakaki, Y. (2000). Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. PNAS 97, 1143-1147.
  158. Hoff, K.G., Silberg, J.J., and Vickery, L.E. (2000). Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proc Natl Acad Sci U S A 97, 7790-7795.
  159. Schilke, B., Voisine, C., Beinert, H., and Craig, E. (1999). Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 96, 10206-10211.
  160. Rouhier, N., Unno, H., Bandyopadhyay, S., Masip, L., Kim, S.K., Hirasawa, M., Gualberto, J.M., Lattard, V., Kusunoki, M., Knaff, D.B., Georgiou, G., Hase, T., Johnson, M.K., and Jacquot, J.P. (2007). Functional, structural, and spectroscopic characterization of a glutathione-ligated [2Fe-2S] cluster in poplar glutaredoxin C1. Proc Natl Acad Sci U S A 104, 7379-7384.
  161. Tong, W.H., Jameson, G.N., Huynh, B.H., and Rouault, T.A. (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, 9762-9767.
  162. Khoroshilova, N., Popescu, C., Munck, E., Beinert, H., and Kiley, P.J. (1997). Iron-sulfur cluster disassembly in the FNR protein of Escherichia coli by O2: [4Fe-4S] to [2Fe-2S] conversion with loss of biological activity. Proc Natl Acad Sci U S A 94, 6087-6092.
  163. Schilke, B., Forster, J., Davis, J., James, P., Walter, W., Laloraya, S., Johnson, J., Miao, B., and Craig, E. (1996). The cold sensitivity of a mutant of Saccharomyces cerevisiae lacking a mitochondrial heat shock protein 70 is suppressed by loss of mitochondrial DNA. J Cell Biol 134, 603-613.
  164. Roy, A., Solodovnikova, N., Nicholson, T., Antholine, W., and Walden, W.E. (2003). A novel eukaryotic factor for cytosolic Fe-S cluster assembly. Embo J 22, 4826-4835. References 157
  165. Ito, H., Fukuda, Y., Murata, K., and Kimura, A. (1983). Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153, 163-168.
  166. Broome-Smith, J.K., and Spratt, B.G. (1982). Deletion of the penicillin-binding protein 6 gene of Escherichia coli. J Bacteriol 152, 904-906.
  167. Bandyopadhyay, S., Gama, F., Molina-Navarro, M.M., Gualberto, J.M., Claxton, R., Naik, S.G., Huynh, B.H., Herrero, E., Jacquot, J.P., Johnson, M.K., and Rouhier, N. (2008). Chloroplast monothiol glutaredoxins as scaffold proteins for the assembly and delivery of [2Fe-2S] clusters. Embo J 27, 1122-1133.
  168. Wang, T., and Craig, E.A. (2008). Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu. J Biol Chem 283, 12674-12679.
  169. Mochel, F., Knight, M.A., Tong, W.H., Hernandez, D., Ayyad, K., Taivassalo, T., Andersen, P.M., Singleton, A., Rouault, T.A., Fischbeck, K.H., and Haller, R.G. (2008). Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet 82, 652-660.
  170. Bych, K., Kerscher, S., Netz, D.J., Pierik, A.J., Zwicker, K., Huynen, M.A., Lill, R., Brandt, U., and Balk, J. (2008). The iron-sulphur protein Ind1 is required for effective complex I assembly. Embo J 27, 1736-1746.
  171. Raulfs, E.C., O'Carroll, I.P., Dos Santos, P.C., Unciuleac, M.C., and Dean, D.R. (2008). In vivo iron-sulfur cluster formation. Proc Natl Acad Sci U S A 105, 8591-8596.
  172. Kumanovics, A., Chen, O.S., Li, L., Bagley, D., Adkins, E.M., Lin, H., Dingra, N.N., Outten, C.E., Keller, G., Winge, D., Ward, D.M., and Kaplan, J. (2008). Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis. J Biol Chem 283, 10276-10286.
  173. Puig, S., Vergara, S.V., and Thiele, D.J. (2008). Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency. Cell Metab 7, 555-564.
  174. Pedro-Segura, E., Vergara, S.V., Rodriguez-Navarro, S., Parker, R., Thiele, D.J., and Puig, S. (2008). The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of succinate dehydrogenase SDH4 mRNA in response to iron deficiency. J Biol Chem 283, 28527-28535.
  175. Andrew, A.J., Song, J.Y., Schilke, B., and Craig, E.A. (2008). Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu. Mol Biol Cell 19, 5259-5266.
  176. Computationally driven, quantitative experiments discover genes required for mitochondrial biogenesis.
  177. Schonauer, M.S., Kastaniotis, A.J., Kursu, V.A., Hiltunen, J.K., and Dieckmann, C.L. (2009). Lipoic acid synthesis and attachment in yeast mitochondria. J Biol Chem 284, 23234-23242.
  178. Rada, P., Smid, O., Sutak, R., Dolezal, P., Pyrih, J., Zarsky, V., Montagne, J.J., Hrdy, I., Camadro, J.M., and Tachezy, J. (2009). The monothiol single-domain glutaredoxin is conserved in the highly reduced mitochondria of Giardia intestinalis. Eukaryot cell 8, 1584-1591.
  179. Li, H., Mapolelo, D.T., Dingra, N.N., Naik, S.G., Lees, N.S., Hoffman, B.M., Riggs-Gelasco, P.J., Huynh, B.H., Johnson, M.K., and Outten, C.E. (2009). The yeast iron regulatory proteins Grx3/4 and Fra2 form heterodimeric complexes containing a [2Fe-2S] cluster with cysteinyl and histidyl ligation. Biochemistry 48, 9569-9581.
  180. Hjort, K., Goldberg, A.V., Tsaousis, A.D., Hirt, R.P., and Embley, T.M. (2010). Diversity and reductive evolution of mitochondria among microbial eukaryotes. Philos Trans R Soc Lond B Biol Sci 365, 713-727.
  181. Rouhier, N., Couturier, J., Johnson, M.K., and Jacquot, J.P. (2010). Glutaredoxins: roles in iron homeostasis. Trends Biochem Sci 35, 43-52.
  182. Ye, H., Jeong, S.Y., Ghosh, M.C., Kovtunovych, G., Silvestri, L., Ortillo, D., Uchida, N., Tisdale, J., Camaschella, C., and Rouault, T.A. (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.
  183. Sheftel, A.D., Stehling, O., Pierik, A.J., Elsasser, H.P., Muhlenhoff, U., Webert, H., Hobler, A., Hannemann, F., Bernhardt, R., and 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, 11775-11780.
  184. Kampinga, H.H., and Craig, E.A. (2010). The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 11, 579-592.
  185. Iannuzzi, C., Adinolfi, S., Howes, B.D., Garcia-Serres, R., Clemancey, M., Latour, J.M., Smulevich, G., and Pastore, A. (2011). The role of CyaY in iron sulfur cluster assembly on the E. coli IscU scaffold protein. PLoS One 6, e21992. References 151
  186. Cameron, J.M., Janer, A., Levandovskiy, V., Mackay, N., Rouault, T.A., Tong, W.H., Ogilvie, I., Shoubridge, E.A., and Robinson, B.H. (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, 486-495.
  187. Yeung, N., Gold, B., Liu, N.L., Prathapam, R., Sterling, H.J., Willams, E.R., and Butland, G. (2011). The E. coli monothiol glutaredoxin GrxD forms homodimeric and heterodimeric FeS cluster containing complexes. Biochemistry 50, 8957-8969.
  188. Ren, Y., Yang, S., Tan, G., Ye, W., Liu, D., Qian, X., Ding, Z., Zhong, Y., Zhang, J., Jiang, D., Zhao, Y., and Lu, J. (2012). Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans. PLoS One 7, e29666.
  189. Rutherford, J.C., and Bird, A.J. (2004). Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot Cell 3, 1-13.
  190. Muhlenhoff, U., Richter, N., Pines, O., Pierik, A.J., and Lill, R. (2011). Specialized Function of Yeast Isa1 and Isa2 Proteins in the Maturation of Mitochondrial [4Fe-4S] Proteins. J Biol Chem 286, 41205-41216.
  191. Sheftel, A.D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.P., Muhlenhoff, U., and Lill, R. (2012). The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation. Mol Biol Cell 23, 1157-1166.
  192. Bridwell-Rabb, J., Iannuzzi, C., Pastore, A., and Barondeau, D.P. (2012). Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis. Biochemistry 51, 2506-2514.
  193. Rawat, S., and Stemmler, T.L. (2011). Key players and their role during mitochondrial iron-sulfur cluster biosynthesis. Chemistry 17, 746-753.
  194. Qi, W., Li, J., Chain, C.Y., Pasquevich, G.A., Pasquevich, A.F., and Cowan, J.A. (2012). Glutathione complexed Fe-S centers. Journal of the American Chemical Society 134, 10745-10748.
  195. Stehling, O., Vashisht, A.A., Mascarenhas, J., Jonsson, Z.O., Sharma, T., Netz, D.J., Pierik, A.J., Wohlschlegel, J.A., and Lill, R. (2012). MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science 337, 195-199.
  196. Shakamuri, P., Zhang, B., and Johnson, M.K. (2012). Monothiol glutaredoxins function in storing and transporting [Fe2S2] clusters assembled on IscU scaffold proteins. J Am Chem Soc 134, 15213-15216.
  197. Li, H., and Outten, C.E. (2012). Monothiol CGFS glutaredoxins and BolA-like proteins: [2Fe-2S] binding partners in iron homeostasis. Biochemistry 51, 4377-4389.
  198. Willems, P., Wanschers, B.F., Esseling, J., Szklarczyk, R., Kudla, U., Duarte, I., Forkink, M., Nooteboom, M., Swarts, H., Gloerich, J., Nijtmans, L., Koopman, W., and Huynen, M.A. (2013). BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion. Antioxid Redox Signal 18, 129-138.
  199. Shi, Y., Ghosh, M., Kovtunovych, G., Crooks, D.R., and Rouault, T.A. (2012). Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis. Biochim Biophys Acta 1823, 484-492.
  200. Vogelstein, B., and Gillespie, D. (1979). Preparative and analytical purification of DNA from agarose. Proc. Natl. Acad. Sci. USA. 76, 615-619.
  201. Yamaguchi-Iwai, Y., Dancis, A., and Klausner, R.D. (1995). AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. Embo J 14, 1231-1239.
  202. Balk, J., Pierik, A.J., Netz, D.J., Muhlenhoff, U., and Lill, R. (2004). The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins. Embo J 23, 2105-2115.
  203. Holmgren, A. (1976). Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione. PNAS 73, 2275-2279.
  204. Yamaguchi-Iwai, Y., Stearman, R., Dancis, A., and Klausner, R.D. (1996). Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast. Embo J 15, 3377-3384.
  205. Hausmann, A., Aguilar Netz, D.J., Balk, J., Pierik, A.J., Muhlenhoff, U., and Lill, R. (2005). The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery. Proc Natl Acad Sci U S A 102, 3266-3271.
  206. Jensen, L.T., and Culotta, V.C. (2000). Role of Saccharomyces cerevisiae ISA1 and ISA2 in iron homeostasis. Mol Cell Biol 20, 3918-3927.
  207. Portnoy, M.E., Liu, X.F., and Culotta, V.C. (2000). Saccharomyces cerevisiae expresses three functionally distinct homologues of the nramp family of metal transporters. Mol Cell Biol 20, 7893-7902.
  208. Yabe, T., Morimoto, K., Kikuchi, S., Nishio, K., Terashima, I., and Nakai, M. (2004). The Arabidopsis chloroplastic NifU-like protein CnfU, which can act as an iron-sulfur cluster scaffold protein, is required for biogenesis of ferredoxin and photosystem I. Plant Cell 16, 993-1007.
  209. Mortenson, L.E.C., J. E.; Valentine, R. C. (1962). An electron transport factor from Clostridium pasteurianum. Biochem Biophys Res Commun 7, 448-452.
  210. Pelzer, W., Muhlenhoff, U., Diekert, K., Siegmund, K., Kispal, G., and Lill, R. (2000). Mitochondrial Isa2p plays a crucial role in the maturation of cellular iron-sulfur proteins. FEBS Lett 476, 134-139.
  211. Gunshin, H., Allerson, C.R., Polycarpou-Schwarz, M., Rofts, A., Rogers, J.T., Kishi, F., Hentze, M.W., Rouault, T.A., Andrews, N.C., and Hediger, M.A. (2001). Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 509, 309-316.
  212. Kispal, G., Csere, P., Guiard, B., and Lill, R. (1997). The ABC transporter Atm1p is required for mitochondrial iron homeostasis. FEBS Lett 418, 346-350.
  213. Yeh, A.P., Chatelet, C., Soltis, S.M., Kuhn, P., Meyer, J., and Rees, D.C. (2000). Structure of a thioredoxin- like [2Fe-2S] ferredoxin from Aquifex aeolicus. J Mol Biol 300, 587-595.
  214. Puig, S., Askeland, E., and Thiele, D.J. (2005). Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 120, 99-110.
  215. Mesecke, N., Terziyska, N., Kozany, C., Baumann, F., Neupert, W., Hell, K., and Herrmann, J.M. (2005). A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell 121, 1059-1069.
  216. Pomposiello, P.J., and Demple, B. (2001). Redox-operated genetic switches: the SoxR and OxyR transcription factors. Trends Biotechnol 19, 109-114.
  217. Wu, H., Lin, L., Giblin, F., Ho, Y.S., and Lou, M.F. (2011). Glutaredoxin 2 knockout increases sensitivity to oxidative stress in mouse lens epithelial cells. Free radical biology & medicine 51, 2108-2117.
  218. Butland, G., Babu, M., Diaz-Mejia, J.J., Bohdana, F., Phanse, S., Gold, B., Yang, W., Li, J., Gagarinova, A.G., Pogoutse, O., Mori, H., Wanner, B.L., Lo, H., Wasniewski, J., Christopolous, C., Ali, M., Venn, P., Safavi- Naini, A., Sourour, N., Caron, S., Choi, J.Y., Laigle, L., Nazarians-Armavil, A., Deshpande, A., Joe, S., Datsenko, K.A., Yamamoto, N., Andrews, B.J., Boone, C., Ding, H., Sheikh, B., Moreno-Hagelseib, G., Greenblatt, J.F., and Emili, A. (2008). eSGA: E. coli synthetic genetic array analysis. Nature methods 5, 789-795.
  219. Courel, M., Lallet, S., Camadro, J.M., and Blaiseau, P.L. (2005). Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1. Mol Cell Biol 25, 6760-6771.
  220. Balk, J., and Lobreaux, S. (2005). Biogenesis of iron-sulfur proteins in plants. Trends Plant Sci 10, 324-331.
  221. Fontecave, M., Choudens, S.O., Py, B., and Barras, F. (2005). Mechanisms of iron-sulfur cluster assembly: the SUF machinery. J Biol Inorg Chem 10, 713-721.
  222. NfuA, a new factor required for maturing Fe/S proteins in Escherichia coli under oxidative stress and iron starvation conditions. J Biol Chem 283, 14084-14091.
  223. Yoon, H., Zhang, Y., Pain, J., Lyver, E.R., Lesuisse, E., Pain, D., and Dancis, A. (2011). Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria. Biochem J 440, 137-146.
  224. Meyer, Y., Buchanan, B.B., Vignols, F., and Reichheld, J.P. (2009). Thioredoxins and glutaredoxins: unifying elements in redox biology. Annu. Rev. Genet. 43, 335-367.
  225. Py, B., Gerez, C., Angelini, S., Planel, R., Vinella, D., Loiseau, L., Talla, E., Brochier-Armanet, C., Garcia Serres, R., Latour, J.M., Ollagnier-de Choudens, S., Fontecave, M., and Barras, F. (2012). Molecular organization, biochemical function, cellular role and evolution of NfuA, an atypical Fe-S carrier. Mol Microbiol 86, 155-171.
  226. Meyer, J. (2008). Iron-sulfur protein folds, iron-sulfur chemistry, and evolution. J Biol Inorg Chem 13, 157-170.
  227. Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS. Nature Struct Mol Biol 16, 390-396.
  228. Dutkiewicz, R., Marszalek, J., Schilke, B., Craig, E.A., Lill, R., and Muhlenhoff, U. (2006). The hsp70 chaperone ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein isu1p. J Biol Chem 281, 7801-7808.

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