Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells

Journal of Biological Chemistry

Volumn 292, Issue 31, 2017, Pages 12764-12771

  Philpott, Caroline C ^a   Ryu, Moon Suhn ^b   Frey, Avery ^c   Patel, Sarju ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c BIOLEGEND   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL DEATH; ENZYMES; MAMMALS; METAL IONS;

BINDING PROTEINS; DISTRIBUTION OF METAL; EUKARYOTIC CELLS; FERRITIN IRON; MAMMALIAN CELLS; METALLO-PROTEINS; MONOTHIOL GLUTAREDOXIN; SULFUR CLUSTERS;

IRON;

BOLA2 PROTEIN; CHAPERONE; DEOXYHYPUSINE HYDROXYLASE; FERRITIN; FERROPORTIN; GLRX3 PROTEIN; GLUTAREDOXIN; HERC2 PROTEIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON; NUCLEAR RECEPTOR COACTIVATOR; NUCLEAR RECEPTOR COACTIVATOR 4; OXYGENASE; PCBP1 PROTEIN; PCBP2 PROTEIN; SULFUR; UNCLASSIFIED DRUG; APOENZYME; APOFERRITIN; BOLA2 PROTEIN, HUMAN; CARRIER PROTEIN; CATION TRANSPORT PROTEIN; GLRX3 PROTEIN, HUMAN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; IRON SULFUR PROTEIN; METAL TRANSPORTING PROTEIN 1; NCOA4 PROTEIN, HUMAN; PCBP1 PROTEIN, HUMAN; PCBP2 PROTEIN, HUMAN; PROTEIN; RNA BINDING PROTEIN;

AUTOPHAGOSOME; AUTOPHAGY; CELL DIFFERENTIATION; CELL MATURATION; COMPLEX FORMATION; CYTOSOL; ERYTHROID PRECURSOR CELL; HUMAN; INTRACELLULAR TRANSPORT; IRON KINETICS; IRON TRANSPORT; MAMMAL CELL; METALLATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SHORT SURVEY; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; CYTOLOGY; DIMERIZATION; METABOLISM; MOLECULAR MODEL; PROTEIN MULTIMERIZATION; PROTEIN TRANSPORT;

ANIMALS; APOENZYMES; APOFERRITINS; AUTOPHAGY; CARRIER PROTEINS; CATION TRANSPORT PROTEINS; CYTOSOL; DIMERIZATION; ERYTHROID PRECURSOR CELLS; FERRITINS; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEINS; HUMANS; IRON; IRON-SULFUR PROTEINS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MOLECULAR CHAPERONES; NUCLEAR RECEPTOR COACTIVATORS; PROTEIN MULTIMERIZATION; PROTEIN TRANSPORT; PROTEINS; RNA-BINDING PROTEINS;

EID: 85026758063     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R117.791962     Document Type: Short Survey

References (85)

1. Hare, D. J., Grubman, A., Ryan, T. M., Lothian, A., Liddell, J. R., Grimm, R., Matsuda, T., Doble, P. A., Cherny, R. A., Bush, A. I., White, A. R., Masters, C. L., and Roberts, B. R. (2013) Profiling the iron, copper and zinc content in primary neuron and astrocyte cultures by rapid online quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry. Metallomics 5, 1656 –1662
2. Yannone, S. M., Hartung, S., Menon, A. L., Adams, M. W., and Tainer, J. A. (2012) Metals in biology: defining metalloproteomes. Curr. Opin. Biotech-nol. 23, 89 –95
3. Cvetkovic, A., Menon, A. L., Thorgersen, M. P., Scott, J. W., Poole, F. L., 2nd, Jenney, F. E., Jr, Lancaster, W. A., Praissman, J. L., Shanmukh, S., Vaccaro, B. J., Trauger, S. A., Kalisiak, E., Apon, J. V., Siuzdak, G., Yannone, S. M., et al. (2010) Microbial metalloproteomes are largely uncharacter-ized. Nature 466, 779 –782
4. Netz, D. J., Stith, C. M., Stümpfig, M., Köpf, G., Vogel, D., Genau, H. M., Stodola, J. L., Lill, R., Burgers, P. M., and Pierik, A. J. (2011) Eukaryotic DNA polymerases require an iron–sulfur cluster for the formation of active complexes. Nat. Chem. Biol. 8, 125–132
5. 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
6. Xue, X., Ramakrishnan, S. K., Weisz, K., Triner, D., Xie, L., Attili, D., Pant, A., Gyrffy, B., Zhan, M., Carter-Su, C., Hardiman, K. M., Wang, T. D., Dame, M. K., Varani, J., Brenner, D., Fearon, E. R., and Shah, Y. M. (2016) Iron uptake via DMT1 integrates cell cycle with JAK-STAT3 signaling to promote colorectal tumorigenesis. Cell Metab. 24, 447– 461
7. Waldron, K. J., Rutherford, J. C., Ford, D., and Robinson, N. J. (2009) Metalloproteins and metal sensing. Nature 460, 823– 830
8. Lin, S. J., Pufahl, R. A., Dancis, A., O’Halloran, T. V., and Culotta, V. C. (1997) A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport. J. Biol. Chem. 272, 9215–9220
9. Mangani, S., Meyer-Klaucke, W., Moir, A. J., Ranieri-Raggi, M., Martini, D., and Raggi, A. (2003) Characterization of the zinc-binding site of the histidine-proline-rich glycoprotein associated with rabbit skeletal muscle AMP deaminase. J. Biol. Chem. 278, 3176 –3184
10. Pufahl, R. A., Singer, C. P., Peariso, K. L., Lin, S. J., Schmidt, P. J., Fahrni, C. J., Culotta, V. C., Penner-Hahn, J. E., and O’Halloran, T. V. (1997) Metal ion chaperone function of the soluble Cu(I) receptor Atx1 (see comments). Science 278, 853– 856
11. Shi, H., Bencze, K. Z., Stemmler, T. L., and Philpott, C. C. (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320, 1207–1210
12. Chaudhury, A., Chander, P., and Howe, P. H. (2010) Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: focus on hnRNP E1’s multifunctional regulatory roles. RNA 16, 1449 –1462
13. Makeyev, A. V., Chkheidze, A. N., and Liebhaber, S. A. (1999) A set of highly conserved RNA-binding proteins, CP-1 and CP-2, implicated in mRNA stabilization, are coexpressed from an intronless gene and its in-tron-containing paralog. J. Biol. Chem. 274, 24849 –24857
14. Makeyev, A. V., and Liebhaber, S. A. (2002) The poly(C)-binding proteins: a multiplicity of functions and a search for mechanisms. RNA 8, 265–278
15. Ostareck-Lederer, A., and Ostareck, D. H. (2004) Control of mRNA translation and stability in haematopoietic cells: the function of hnRNPs K and E1/E2. Biol. Cell 96, 407– 411
16. Ostareck-Lederer, A., and Ostareck, D. H. (2012) Precision mechanics with multifunctional tools: how hnRNP K and hnRNPs E1/E2 contribute to post-transcriptional control of gene expression in hematopoiesis. Curr. Protein Pept. Sci. 13, 391– 400
17. Arosio, P., and Levi, S. (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim. Biophys. Acta 1800, 783–792
18. Epsztejn, S., Kakhlon, O., Glickstein, H., Breuer, W., and Cabantchik, I. (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal. Biochem. 248, 31– 40
19. Frey, A. G., Nandal, A., Park, J. H., Smith, P. M., Yabe, T., Ryu, M. S., Ghosh, M. C., Lee, J., Rouault, T. A., Park, M. H., and Philpott, C. C. (2014) Iron chaperones PCBP1 and PCBP2 mediate the metallation of the di-nuclear iron enzyme deoxyhypusine hydroxylase. Proc. Natl. Acad. Sci. U.S.A. 111, 8031– 8036
20. Nandal, A., Ruiz, J. C., Subramanian, P., Ghimire-Rijal, S., Sinnamon, R. A., Stemmler, T. L., Bruick, R. K., and Philpott, C. C. (2011) Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2. Cell Metab. 14, 647– 657
21. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., and Hediger, M. A. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482– 488
22. Wang, C. Y., Jenkitkasemwong, S., Duarte, S., Sparkman, B. K., Shawki, A., Mackenzie, B., and Knutson, M. D. (2012) ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. J. Biol. Chem. 287, 34032–34043
23. Liuzzi, J. P., Aydemir, F., Nam, H., Knutson, M. D., and Cousins, R. J. (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc. Natl. Acad. Sci. U.S.A. 103, 13612–13617
24. Yanatori, I., Yasui, Y., Tabuchi, M., and Kishi, F. (2014) Chaperone protein involved in transmembrane transport of iron. Biochem. J. 462, 25–37
25. Ryu, M. S., Zhang, D., Protchenko, O., Shakoury-Elizeh, M., and Philpott, C. C. (2017) PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis. J. Clin. Invest. 127, 1786 –1797
26. Abboud, S., and Haile, D. J. (2000) A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275, 19906–19912
27. Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., et al. (2000) Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403, 776 –781
28. McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., and Simpson, R. J. (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell 5, 299 –309
29. Yanatori, I., Richardson, D. R., Imada, K., and Kishi, F. (2016) Iron export through the transporter ferroportin 1 is modulated by the iron chaperone PCBP2. J. Biol. Chem. 291, 17303–17318
30. Arosio, P., Elia, L., and Poli, M. (2017) Ferritin, cellular iron storage and regulation. IUBMB Life 69, 414 – 422
31. Carmona, F., Poli, M., Bertuzzi, M., Gianoncelli, A., Gangemi, F., and Arosio, P. (2017) Study of ferritin self-assembly and heteropolymer formation by the use of fluorescence resonance energy transfer (FRET) technology. Biochim. Biophys. Acta 1861, 522–532
32. Leidgens, S., Bullough, K. Z., Shi, H., Li, F., Shakoury-Elizeh, M., Yabe, T., Subramanian, P., Hsu, E., Natarajan, N., Nandal, A., Stemmler, T. L., and Philpott, C. C. (2013) Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin. J. Biol. Chem. 288, 17791–17802
33. Dever, T. E., Gutierrez, E., and Shin, B. S. (2014) The hypusine-containing translation factor eIF5A. Crit. Rev. Biochem. Mol. Biol. 49, 413– 425
34. Vu, V. V., Emerson, J. P., Martinho, M., Kim, Y. S., Münck, E., Park, M. H., and Que, L., Jr. (2009) Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O2 with a nonheme diiron center. Proc. Natl. Acad. Sci. U.S.A. 106, 14814 –14819
35. Costas, M., Mehn, M. P., Jensen, M. P., and Que, L., Jr. (2004) Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. Chem. Rev. 104, 939 –986
36. Tinberg, C. E., and Lippard, S. J. (2009) Revisiting the mechanism of dioxygen activation in soluble methane monooxygenase from M. capsulatus (Bath): evidence for a multi-step, proton-dependent reaction pathway. Biochemistry 48, 12145–12158
37. Palis, J. (2014) Primitive and definitive erythropoiesis in mammals. Front. Physiol. 5, 3
38. Ganz, T., and Nemeth, E. (2012) Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb. Perspect. Med. 2, a011668
39. Konijn, A. M., Hershko, C., and Izak, G. (1979) Ferritin synthesis and iron uptake in developing erythroid cells. Am. J. Hematol. 6, 373–379
40. Darshan, D., Vanoaica, L., Richman, L., Beermann, F., and Kühn, L. C. (2009) Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage. Hepatology 50, 852– 860
41. Kidane, T. Z., Sauble, E., and Linder, M. C. (2006) Release of iron from ferritin requires lysosomal activity. Am. J. Physiol. Cell Physiol. 291, C445–C455
42. Zhang, Y., Mikhael, M., Xu, D., Li, Y., Soe-Lin, S., Ning, B., Li, W., Nie, G., Zhao, Y., and Ponka, P. (2010) Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit. Antioxid. Redox Signal. 13, 999 –1009
43. Asano, T., Komatsu, M., Yamaguchi-Iwai, Y., Ishikawa, F., Mizushima, N., and Iwai, K. (2011) Distinct mechanisms of ferritin delivery to lysosomes in iron-depleted and iron-replete cells. Mol. Cell. Biol. 31, 2040 –2052
44. Dowdle, W. E., Nyfeler, B., Nagel, J., Elling, R. A., Liu, S., Triantafellow, E., Menon, S., Wang, Z., Honda, A., Pardee, G., Cantwell, J., Luu, C., Cornella-Taracido, I., Harrington, E., Fekkes, P., et al. (2014) Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 16, 1069 –1079
45. Mancias, J. D., Wang, X., Gygi, S. P., Harper, J. W., and Kimmelman, A. C. (2014) Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509, 105–109
46. Heinlein, C. A., Ting, H. J., Yeh, S., and Chang, C. (1999) Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor . J. Biol. Chem. 274, 16147–16152
47. Yeh, S., and Chang, C. (1996) Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc. Natl. Acad. Sci. U.S.A. 93, 5517–5521
48. Mancias, J. D., Pontano Vaites, L., Nissim, S., Biancur, D. E., Kim, A. J., Wang, X., Liu, Y., Goessling, W., Kimmelman, A. C., and Harper, J. W. (2015) Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife 10.7554/eLife.10308
49. Nilsson, R., Schultz, I. J., Pierce, E. L., Soltis, K. A., Naranuntarat, A., Ward, D. M., Baughman, J. M., Paradkar, P. N., Kingsley, P. D., Culotta, V. C., Kaplan, J., Palis, J., Paw, B. H., and Mootha, V. K. (2009) Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metab. 10, 119 –130
50. Bellelli, R., Federico, G., Matte’, A., Colecchia, D., Iolascon, A., Chiariello, M., Santoro, M., De Franceschi, L., and Carlomagno, F. (2016) NCOA4 deficiency impairs systemic iron homeostasis. Cell Rep. 14, 411– 421
51. Sheftel, A. D., Zhang, A. S., Brown, C., Shirihai, O. S., and Ponka, P. (2007) Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 110, 125–132
52. Lill, R., Dutkiewicz, R., Freibert, S. A., Heidenreich, T., Mascarenhas, J., Netz, D. J., Paul, V. D., Pierik, A. J., Richter, N., Stümpfig, M., Srinivasan, V., Stehling, O., and Mühlenhoff, U. (2015) The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins. Eur. J. Cell Biol. 94, 280 –291
53. Rouhier, N., Couturier, J., Johnson, M. K., and Jacquot, J. P. (2010) Glutaredoxins: roles in iron homeostasis. Trends Biochem. Sci. 35, 43–52
54. Mühlenhoff, U., Gerber, J., Richhardt, N., and Lill, R. (2003) Components involved in assembly and dislocation of iron–sulfur clusters on the scaffold protein Isu1p. EMBO J. 22, 4815– 4825
55. Rodríguez-Manzaneque, M. T., Tamarit, J., Bellí, 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
56. 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., et al. (2005) Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436, 1035–1039
57. Mühlenhoff, U., Molik, S., Godoy, J. R., Uzarska, M. A., Richter, N., Seu-bert, 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
58. 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 heterodi-meric complexes containing a [2Fe-2S] cluster with cysteinyl and histidyl ligation. Biochemistry 48, 9569 –9581
59. Banci, L., Ciofi-Baffoni, S., Gajda, K., Muzzioli, R., Peruzzini, R., and Winkelmann, J. (2015) N-terminal domains mediate [2Fe-2S] cluster transfer from glutaredoxin-3 to anamorsin. Nat. Chem. Biol. 11, 772–778
60. Li, H., Mapolelo, D. T., Randeniya, S., Johnson, M. K., and Outten, C. E. (2012) Human glutaredoxin 3 forms [2Fe-2S]-bridged complexes with human BolA2. Biochemistry 51, 1687–1696
61. Frey, A. G., Palenchar, D. J., Wildemann, J. D., and Philpott, C. C. (2016) A glutaredoxin-BolA complex serves as an iron–sulfur cluster chaperone for the cytosolic cluster assembly machinery. J. Biol. Chem. 292, M116.744946
62. Haunhorst, P., Hanschmann, E. M., Bräutigam, L., Stehling, O., Hoffmann, B., Mühlenhoff, U., Lill, R., Berndt, C., and Lillig, C. H. (2013) Crucial function of vertebrate glutaredoxin 3 (PICOT) in iron homeostasis and hemoglobin maturation. Mol. Biol. Cell 24, 1895–1903
63. 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
64. Aldea, M., Hernández-Chico, C., de la Campa, A. G., Kushner, S. R., and Vicente, M. (1988) Identification, cloning, and expression of bolA, an ftsZ-dependent morphogene of Escherichia coli. J. Bacteriol. 170, 5169 –5176
65. 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 dehydroge-nase enzymes. Am. J. Hum. Genet. 89, 486 – 495
66. Melber, A., Na, U., Vashisht, A., Weiler, B. D., Lill, R., Wohlschlegel, J. A., and Winge, D. R. (2016) Role of Nfu1 and Bol3 in iron–sulfur cluster transfer to mitochondrial clients. eLife 5, e15991
67. Uzarska, M. A., Nasta, V., Weiler, B. D., Spantgar, F., Ciofi-Baffoni, S., Saviello, M. R., Gonnelli, L., Mühlenhoff, U., Banci, L., and Lill, R. (2016) Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron–sulfur proteins. eLife 5, e16673
68. Kumánovics, 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
69. Li, H., Mapolelo, D. T., Dingra, N. N., Keller, G., Riggs-Gelasco, P. J., Winge, D. R., Johnson, M. K., and Outten, C. E. (2011) Histidine 103 in Fra2 is an iron–sulfur cluster ligand in the [2Fe-2S] Fra2-Grx3 complex and is required for in vivo iron signaling in yeast. J. Biol. Chem. 286, 867–876
70. 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
71. Poor, C. B., Wegner, S. V., Li, H., Dlouhy, A. C., Schuermann, J. P., Sanishvili, R., Hinshaw, J. R., Riggs-Gelasco, P. J., Outten, C. E., and He, C. (2014) Molecular mechanism and structure of the Saccharomyces cerevisiae iron regulator Aft2. Proc. Natl. Acad. Sci. U.S.A. 111, 4043– 4048
72. 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
73. Ueta, R., Fujiwara, N., Iwai, K., and Yamaguchi-Iwai, Y. (2007) Mechanism underlying the iron-dependent nuclear export of the iron-responsive transcription factor Aft1p in Saccharomyces cerevisiae. Mol. Biol. Cell 18, 2980–2990
74. Encinar del Dedo, J., Gabrielli, N., Carmona, M., Ayté, J., and Hidalgo, E. (2015) A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast. PLoS Genet. 11, e1005106
75. Jbel, M., Mercier, A., and Labbé, S. (2011) Grx4 monothiol glutaredoxin is required for iron limitation-dependent inhibition of Fep1. Eukaryot. Cell 10, 629 – 645
76. Mercier, A., and Labbé, S. (2009) Both Php4 function and subcellular localization are regulated by iron via a multistep mechanism involving the glutaredoxin Grx4 and the exportin Crm1. J. Biol. Chem. 284, 20249 –20262
77. Vachon, P., Mercier, A., Jbel, M., and Labbé, S. (2012) The monothiol glutaredoxin Grx4 exerts an iron-dependent inhibitory effect on Php4 function. Eukaryot. Cell 11, 806 – 819
78. Banci, L., Camponeschi, F., Ciofi-Baffoni, S., and Muzzioli, R. (2015) Elucidating the molecular function of human BOLA2 in GRX3-depen-dent anamorsin maturation pathway. J Am. Chem. Soc. 137, 16133–16143
79. Banci, L., Bertini, I., Calderone, V., Ciofi-Baffoni, S., Giachetti, A., Jaiswal, D., Mikolajczyk, M., Piccioli, M., and Winkelmann, J. (2013) Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis. Proc. Natl. Acad. Sci. U.S.A. 110, 7136 –7141
80. Banci, L., Ciofi-Baffoni, S., Mikolajczyk, M., Winkelmann, J., Bill, E., and Pandelia, M. E. (2013) Human anamorsin binds [2Fe-2S] clusters with unique electronic properties. J. Biol. Inorg. Chem. 18, 883– 893
81. Netz, D. J., Genau, H. M., Weiler, B. D., Bill, E., Pierik, A. J., and Lill, R. (2016) The conserved Dre2 uses essential [2Fe-2S] and [4Fe-4S] clusters for function in cytosolic iron–sulfur protein assembly. Biochem. J. 473, 2073–2085
82. Netz, D. J., Stümpfig, M., Doré, C., Mühlenhoff, U., Pierik, A. J., and Lill, R. (2010) Tah18 transfers electrons to Dre2 in cytosolic iron–sulfur protein biogenesis. Nat. Chem. Biol. 6, 758 –765
83. Zhang, Y., Lyver, E. R., Nakamaru-Ogiso, E., Yoon, H., Amutha, B., Lee, D. W., Bi, E., Ohnishi, T., Daldal, F., Pain, D., and Dancis, A. (2008) Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis. Mol. Cell. Biol. 28, 5569 –5582
84. Lipper, C. H., Paddock, M. L., Onuchic, J. N., Mittler, R., Nechushtai, R., and Jennings, P. A. (2015) Cancer-related NEET proteins transfer 2Fe-2S clusters to anamorsin, a protein required for cytosolic iron–sulfur cluster biogenesis. PLoS One 10, e0139699
85. Tan, G., Liu, D., Pan, F., Zhao, J., Li, T., Ma, Y., Shen, B., and Lyu, J. (2016) His-87 ligand in mitoNEET is crucial for the transfer of iron sulfur clusters from mitochondria to cytosolic aconitase. Biochem. Biophys. Res. Com-mun. 470, 226 –232