Fe–S cluster assembly in the supergroup Excavata

Roger AJ, Muñoz-Gómez SA, Kamikawa R (2017) The origin and diversification of mitochondria. Curr Biol 27:R1177–R1192. https://doi.org/10.1016/j.cub.2017.09.015 Maguire F, Richards TA (2014) Organelle evolution: a mosaic of “mitochondrial” functions. Curr Biol 24:R518–R520. https://doi.org/10.1016/j.cub.2014.03.075 Lill R (2009) Function and biogenesis of iron–sulphur proteins. Nature 460:831–838. https://doi.org/10.1038/nature08301 Verner Z, Basu S, Benz C et al (2015) Malleable mitochondrion of Trypanosoma brucei. Int Rev Cell Mol Biol 315:73–151. https://doi.org/10.1016/bs.ircmb.2014.11.001 Müller M, Mentel M, van Hellemond JJ et al (2012) Biochemistry and evolution of anaerobic energy metabolism in eukaryotes. Microbiol Mol Biol Rev 76:444–495. https://doi.org/10.1128/MMBR.05024-11 Müller M (1993) The hydrogenosome. J Gen Microbiol 139:2879–2889 Lill R, Kispal G (2000) Maturation of cellular Fe–S proteins: an essential function of mitochondria. Trends Biochem Sci 25:352–356 Adl SM, Simpson AGB, Lane CE et al (2012) The revised classification of eukaryotes. J Eukaryot Microbiol 59:429–514. https://doi.org/10.1111/j.1550-7408.2012.00644.x Takahashi Y, Tokumoto U (2002) A third bacterial system for the assembly of iron–sulfur clusters with homologs in archaea and plastids. J Biol Chem 277:28380–28383. https://doi.org/10.1074/jbc.C200365200 Jacobson MR, Cash VL, Weiss MC et al (1989) Biochemical and genetic analysis of the nifUSVWZM cluster from Azotobacter vinelandii. Mol Gen Genet 219:49–57 Loiseau L, Ollagnier de Choudens S, Lascoux D et al (2005) Analysis of the heteromeric CsdA–CsdE cysteine desulfurase, assisting Fe–S cluster biogenesis in Escherichia coli. J Biol Chem 280:26760–26769. https://doi.org/10.1074/jbc.M504067200 Stairs CW, Leger MM, Roger AJ (2015) Diversity and origins of anaerobic metabolism in mitochondria and related organelles. Philos Trans R Soc Lond B Biol Sci 370:20140326. https://doi.org/10.1098/rstb.2014.0326 Stairs CW, Eme L, Brown MW et al (2014) A SUF Fe–S cluster biogenesis system in the mitochondrion-related organelles of the anaerobic protist Pygsuia. Curr Biol 24:1176–1186. https://doi.org/10.1016/j.cub.2014.04.033 Lill R, Dutkiewicz R, Freibert SA et al (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. https://doi.org/10.1016/j.ejcb.2015.05.002 Stehling O, Mascarenhas J, Vashisht AA et al (2013) Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron–sulfur proteins. Cell Metab 18:187–198. https://doi.org/10.1016/j.cmet.2013.06.015 Paul VD, Lill R (2015) Biogenesis of cytosolic and nuclear iron–sulfur proteins and their role in genome stability. BBA-Mol Cell Res 1853:1528–1539. https://doi.org/10.1016/j.bbamcr.2014.12.018 Balk J, Pilon M (2011) Ancient and essential: the assembly of iron–sulfur clusters in plants. Trends Plant Sci 16:218–226. https://doi.org/10.1016/j.tplants.2010.12.006 Barras F, Loiseau L, Py B (2005) How Escherichia coli and Saccharomyces cerevisiae build Fe/S proteins. Adv Microb Physiol 50:41–101. https://doi.org/10.1016/S0065-2911(05)50002-X Roche B, Aussel L, Ezraty B et al (2013) Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochim Biophys Acta 1827:455–469. https://doi.org/10.1016/j.bbabio.2012.12.010 Basu S, Netz DJ, Haindrich AC et al (2014) Cytosolic iron–sulphur protein assembly is functionally conserved and essential in procyclic and bloodstream Trypanosoma brucei. Mol Microbiol 93:897–910. https://doi.org/10.1111/mmi.12706 Iwasaki T (2010) Iron–sulfur world in aerobic and hyperthermoacidophilic archaea Sulfolobus. Archaea 2010:1–14. https://doi.org/10.1155/2010/842639 Tsaousis AD, Ollagnier de Choudens S, Gentekaki E et al (2012) Evolution of Fe/S cluster biogenesis in the anaerobic parasite Blastocystis. Proc Natl Acad Sci USA 109:10426–10431. https://doi.org/10.1073/pnas.1116067109 Karnkowska A, Vacek V, Zubácová Z et al (2016) A eukaryote without a mitochondrial organelle. Curr Biol 26:1274–1284. https://doi.org/10.1016/j.cub.2016.03.053 Tachezy J, Sánchez LB, Müller M (2001) Mitochondrial type iron–sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS. Mol Biol Evol 18:1919–1928. https://doi.org/10.1093/oxfordjournals.molbev.a003732 Freibert SA, Goldberg AV, Hacker C et al (2016) Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis. Nat Commun 8:1–12. https://doi.org/10.1038/ncomms13932 Dellibovi-Ragheb TA, Gisselberg JE, Prigge ST (2013) Parasites FeS up: iron–sulfur cluster biogenesis in eukaryotic pathogens. PLoS Pathog 9:e1003227. https://doi.org/10.1371/journal.ppat.1003227 Hjort K, Goldberg AV, Tsaousis AD et al (2010) Diversity and reductive evolution of mitochondria among microbial eukaryotes. Philos Trans R Soc Lond B Biol Sci 365:713–727. https://doi.org/10.1073/pnas.90.7.2754 Leger MM, Kolísko M, Kamikawa R et al (2017) Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes. Nat Ecol Evol 1:0092. https://doi.org/10.1038/s41559-017-0092 Yan R, Konarev PV, Iannuzzi C et al (2013) Ferredoxin competes with bacterial frataxin in binding to the desulfurase IscS. J Biol Chem 288:24777–24787. https://doi.org/10.1074/jbc.M113.480327 Ayala-Castro C, Saini A, Outten FW (2008) Fe–S cluster assembly pathways in bacteria. Microbiol Mol Biol Rev 72:110–125. https://doi.org/10.1128/mmbr.00034-07 (table of contents) Ollagnier-de-Choudens S, Mattioli T, Takahashi Y, Fontecave M (2001) Iron–sulfur cluster assembly: characterization of IscA and evidence for a specific and functional complex with ferredoxin. J Biol Chem 276:22604–22607. https://doi.org/10.1074/jbc.M102902200 Krebs C, Agar JN, Smith AD et al (2001) IscA, an alternate scaffold for Fe–S cluster biosynthesis. Biochemistry 40:14069–14080. https://doi.org/10.1021/bi015656z Vickery LE, Cupp-Vickery JR (2008) Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron–sulfur protein maturation. Crit Rev Biochem Mol Biol 42:95–111. https://doi.org/10.1080/10409230701322298 Silberg JJ, Tapley TL, Hoff KG, Vickery LE (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. https://doi.org/10.1074/jbc.M410117200 Reyda MR, Fugate CJ, Jarrett JT (2009) A complex between biotin synthase and the iron–sulfur cluster assembly chaperone HscA that enhances in vivo cluster assembly. Biochemistry 48:10782–10792. https://doi.org/10.1021/bi901393t Bonomi F, Iametti S, Morleo A et al (2008) Studies on the mechanism of catalysis of iron–sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry 47:12795–12801. https://doi.org/10.1021/bi801565j Chandramouli K, Johnson MK (2006) HscA and HscB stimulate [2Fe–2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 45:11087–11095. https://doi.org/10.1021/bi061237w Hoff KG, Silberg JJ, Vickery LE (2000) Interaction of the iron–sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proc Natl Acad Sci USA 97:7790–7795. https://doi.org/10.1073/pnas.130201997 Bonomi F, Iametti S, Morleo A et al (2011) Facilitated transfer of IscU-[2Fe2S] clusters by chaperone-mediated ligand exchange. Biochemistry 50:9641–9650. https://doi.org/10.1021/bi201123z Agar JN, Krebs C, Frazzon J et al (2000) IscU as a scaffold for iron–sulfur cluster biosynthesis: sequential assembly of [2Fe–2S] and [4Fe–4S] clusters in IscU. Biochemistry 39:7856–7862. https://doi.org/10.1021/bi000931n Chandramouli K, Unciuleac M-C, Naik S et al (2007) Formation and properties of [4Fe–4S] clusters on the IscU scaffold protein. Biochemistry 46:6804–6811. https://doi.org/10.1021/bi6026659 Adinolfi S, Iannuzzi C, Prischi F et al (2009) Bacterial frataxin CyaY is the gatekeeper of iron–sulfur cluster formation catalyzed by IscS. Nat Struct Mol Biol 16:390–396. https://doi.org/10.1038/nsmb.1579 Loiseau L, Ollagnier de Choudens S, Nachin L et al (2003) Biogenesis of Fe–S cluster by the bacterial Suf system: SufS and SufE form a new type of cysteine desulfurase. J Biol Chem 278:38352–38359. https://doi.org/10.1074/jbc.M305953200 Outten FW, Djaman O, Storz G (2004) A suf operon requirement for Fe–S cluster assembly during iron starvation in Escherichia coli. Mol Microbiol 52:861–872. https://doi.org/10.1111/j.1365-2958.2004.04025.x Outten FW, Wood MJ, Muñoz FM, Storz G (2003) The SufE protein and the SufBCD complex enhance SufS cysteine desulfurase activity as part of a sulfur transfer pathway for Fe–S cluster assembly in Escherichia coli. J Biol Chem 278:45713–45719. https://doi.org/10.1074/jbc.M308004200 Mihara H, Esaki N (2002) Bacterial cysteine desulfurases: their function and mechanisms. Appl Microbiol Biotechnol 60:12–23. https://doi.org/10.1007/s00253-002-1107-4 Layer G, Gaddam SA, Ayala-Castro CN et al (2007) SufE transfers sulfur from SufS to SufB for iron–sulfur cluster assembly. J Biol Chem 282:13342–13350. https://doi.org/10.1074/jbc.M608555200 Wollers S, Layer G, Garcia Serres R et al (2010) Iron–sulfur (Fe–S) cluster assembly: the SufBCD complex is a new type of Fe–S scaffold with a flavin redox cofactor. J Biol Chem 285:23331–23341. https://doi.org/10.1074/jbc.M110.127449 Chahal HK, Outten FW (2012) Separate FeS scaffold and carrier functions for SufB2C2 and SufA during in vitro maturation of [2Fe2S] Fdx. J Inorg Biochem 116:126–134. https://doi.org/10.1016/j.jinorgbio.2012.06.008 Saini A, Mapolelo DT, Chahal HK et al (2010) SufD and SufC ATPase activity are required for iron acquisition during in vivo Fe–S cluster formation on SufB. Biochemistry 49:9402–9412. https://doi.org/10.1021/bi1011546 Nachin L, Loiseau L, Expert D, Barras F (2003) SufC: an unorthodox cytoplasmic ABC/ATPase required for [Fe–S] biogenesis under oxidative stress. EMBO J 22:427–437. https://doi.org/10.1093/emboj/cdg061 Hirabayashi K, Yuda E, Tanaka N et al (2015) Functional dynamics revealed by the structure of the SufBCD complex, a novel ATP-binding cassette (ABC) protein that serves as a scaffold for iron–sulfur cluster biogenesis. J Biol Chem 290:29717–29731. https://doi.org/10.1074/jbc.M115.680934 Vinella D, Brochier-Armanet C, Loiseau L et al (2009) Iron–sulfur (Fe/S) protein biogenesis: phylogenomic and genetic studies of A-type carriers. PLoS Genet 5:e1000497. https://doi.org/10.1371/journal.pgen.1000497 Chahal HK, Dai Y, Saini A et al (2009) The SufBCD Fe–S scaffold complex interacts with SufA for Fe–S cluster transfer. Biochemistry 48:10644–10653. https://doi.org/10.1021/bi901518y Outten FW (2015) Recent advances in the Suf Fe–S cluster biogenesis pathway: beyond the Proteobacteria. BBA Mol Cell Res 1853:1464–1469. https://doi.org/10.1016/j.bbamcr.2014.11.001 Yang J, Bitoun JP, Ding H (2006) Interplay of IscA and IscU in biogenesis of iron–sulfur clusters. J Biol Chem 281:27956–27963. https://doi.org/10.1074/jbc.M601356200 Selbach BP, Chung AH, Scott AD et al (2013) Fe–S cluster biogenesis in Gram-positive bacteria: SufU is a zinc-dependent sulfur transfer protein. Biochemistry 53:152–160. https://doi.org/10.1021/bi4011978 Albrecht AG, Netz DJA, Miethke M et al (2010) SufU is an essential iron–sulfur cluster scaffold protein in Bacillus subtilis. J Bacteriol 192:1643–1651. https://doi.org/10.1128/JB.01536-09 Riboldi GP, de Oliveira JS, Frazzon J (2011) Enterococcus faecalis SufU scaffold protein enhances SufS desulfurase activity by acquiring sulfur from its cysteine-153. BBA Proteins Proteom 1814:1910–1918. https://doi.org/10.1016/j.bbapap.2011.06.016 Mansy SS, Wu G, Surerus KK, Cowan JA (2002) Iron–sulfur cluster biosynthesis. Thermatoga maritima IscU is a structured iron–sulfur cluster assembly protein. J Biol Chem 277:21397–21404. https://doi.org/10.1074/jbc.M201439200 Huet G, Daffe M, Saves I (2005) Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe–S] cluster assembly: evidence for its implication in the pathogen’s survival. J Bacteriol 187:6137–6146. https://doi.org/10.1128/JB.187.17.6137-6146.2005 Olson JW, Agar JN, Johnson MK, Maier RJ (2000) Characterization of the NifU and NifS Fe–S cluster formation proteins essential for viability in Helicobacter pylori. Biochemistry 39:16213–16219. https://doi.org/10.1021/bi001744s Rincon-Enriquez G, Crété P, Barras F, Py B (2008) Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions. Mol Microbiol 67:1257–1273. https://doi.org/10.1111/j.1365-2958.2008.06118.x Glasner JD, Yang C-H, Reverchon S et al (2011) Genome sequence of the plant-pathogenic bacterium Dickeya dadantii 3937. J Bacteriol 193:2076–2077. https://doi.org/10.1128/JB.01513-10 Arnold W, Rump A, Klipp W et al (1988) Nucleotide sequence of a 24,206-base-pair DNA fragment carrying the entire nitrogen fixation gene cluster of Klebsiella pneumoniae. J Mol Biol 203:715–738 Frazzon J, Dean DR (2003) Formation of iron–sulfur clusters in bacteria: an emerging field in bioinorganic chemistry. Curr Opin Chem Biol 7:166–173. https://doi.org/10.1016/S1367-5931(03)00021-8 Curatti L, Ludden PW, Rubio LM (2006) NifB-dependent in vitro synthesis of the iron–molybdenum cofactor of nitrogenase. Proc Natl Acad Sci USA 103:5297–5301. https://doi.org/10.1073/pnas.0601115103 Evans DJ, Jones R, Woodley PR et al (1991) Nucleotide sequence and genetic analysis of the Azotobacter chroococcum nifUSVWZM gene cluster, including a new gene (nifP) which encodes a serine acetyltransferase. J Bacteriol 173:5457–5469 Mihara H, Kurihara T, Yoshimura T et al (1997) Cysteine sulfinate desulfinase, a NIFS-like protein of Escherichia coli with selenocysteine lyase and cysteine desulfurase activities. Gene cloning, purification, and characterization of a novel pyridoxal enzyme. J Biol Chem 272:22417–22424 Mihara H, Maeda M, Fujii T et al (1999) A nifS-like gene, csdB, encodes an Escherichia coli counterpart of mammalian selenocysteine lyase. Gene cloning, purification, characterization and preliminary X-ray crystallographic studies. J Biol Chem 274:14768–14772 Mihara H, Kurihara T, Yoshimura T, Esaki N (2000) Kinetic and mutational studies of three NifS homologs from Escherichia coli: mechanistic difference between l-cysteine desulfurase and l-selenocysteine lyase reactions. J Biochem 127:559–567 Fontecave M, Ollagnier de Choudens S (2008) Iron–sulfur cluster biosynthesis in bacteria: mechanisms of cluster assembly and transfer. Arch Biochem Biophys 474:226–237. https://doi.org/10.1016/j.abb.2007.12.014 Trotter V, Vinella D, Loiseau L et al (2009) The CsdA cysteine desulphurase promotes Fe/S biogenesis by recruiting Suf components and participates to a new sulphur transfer pathway by recruiting CsdL (ex-YgdL), a ubiquitin-modifying-like protein. Mol Microbiol 74:1527–1542. https://doi.org/10.1111/j.1365-2958.2009.06954.x Ali V, Nozaki T (2013) Iron–sulphur clusters, their biosynthesis, and biological functions in protozoan parasites. Adv Parasitol 83:1–92. https://doi.org/10.1016/B978-0-12-407705-8.00001-X Kumar B, Chaubey S, Shah P et al (2011) Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an iron–sulphur cluster biogenesis pathway in the apicoplast of Plasmodium falciparum. Int J Parasitol 41:991–999. https://doi.org/10.1016/j.ijpara.2011.05.006 Nývltová E, Sutak R, Harant K et al (2013) NIF-type iron–sulfur cluster assembly system is duplicated and distributed in the mitochondria and cytosol of Mastigamoeba balamuthi. Proc Natl Acad Sci USA 110:7371–7376. https://doi.org/10.1073/pnas.1219590110 Ali V, Shigeta Y, Tokumoto U et al (2004) An intestinal parasitic protist, Entamoeba histolytica, possesses a non-redundant nitrogen fixation-like system for iron–sulfur cluster assembly under anaerobic conditions. J Biol Chem 279:16863–16874. https://doi.org/10.1074/jbc.M313314200 Poliak P, Van Hoewyk D, Oborník M et al (2009) Functions and cellular localization of cysteine desulfurase and selenocysteine lyase in Trypanosoma brucei. FEBS J 277:383–393. https://doi.org/10.1111/j.1742-4658.2009.07489.x Richards TA, van der Giezen M (2006) Evolution of the Isd11–IscS complex reveals a single alpha-proteobacterial endosymbiosis for all eukaryotes. Mol Biol Evol 23:1341–1344. https://doi.org/10.1093/molbev/msl001 Wiedemann N, Urzica E, Guiard B et al (2006) Essential role of Isd11 in mitochondrial iron–sulfur cluster synthesis on Isu scaffold proteins. EMBO J 25:184–195. https://doi.org/10.1038/sj.emboj.7600906 Shi Y, Ghosh MC, Tong W-H, Rouault TA (2009) Human ISD11 is essential for both iron–sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Hum Mol Gen 18:3014–3025. https://doi.org/10.1093/hmg/ddp239 Friemel M, Marelja Z, Li K, Leimkühler 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 56:1797–1808. https://doi.org/10.1021/acs.biochem.6b01239 Biederbick A, Stehling O, Rösser R et al (2006) Role of human mitochondrial Nfs1 in cytosolic iron–sulfur protein biogenesis and iron regulation. Mol Cell Biol 26:5675–5687. https://doi.org/10.1128/MCB.00112-06 Van Vranken JG, Jeong M-Y, Wei P et al (2016) The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. Elife. https://doi.org/10.7554/eLife.17828 Cory SA, Van Vranken JG, Brignole EJ et al (2017) Structure of human Fe–S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP–ISD11 interactions. Proc Natl Acad Sci USA 114:E5325–E5334. https://doi.org/10.1073/pnas.1702849114 Boniecki MT, Freibert SA, Mühlenhoff U et al (2017) Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex. Nat Commun 8:1287. https://doi.org/10.1038/s41467-017-01497-1 Sheftel AD, Stehling O, Pierik AJ et al (2010) Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis. Proc Natl Acad Sci USA 107:11775–11780. https://doi.org/10.1073/pnas.1004250107 Shan Y, Cortopassi G (2012) HSC20 interacts with frataxin and is involved in iron–sulfur cluster biogenesis and iron homeostasis. Hum Mol Gen 21:1457–1469. https://doi.org/10.1093/hmg/ddr582 Beilschmidt LK, Ollagnier de Choudens S, Fournier M et al (2017) ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo. Nat Commun 8:15124. https://doi.org/10.1038/ncomms15124 Ciofi-Baffoni S, Nasta V, Banci L (2018) Protein networks in the maturation of human iron–sulfur proteins. Metallomics 10:49–72. https://doi.org/10.1039/c7mt00269f Tong W-H, Rouault T (2000) Distinct iron–sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J 19:5692–5700. https://doi.org/10.1093/emboj/19.21.5692 Uhrigshardt H, Singh A, Kovtunovych G et al (2010) Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron–sulfur cluster biogenesis. Hum Mol Gen 19:3816–3834. https://doi.org/10.1093/hmg/ddq301 Uhrigshardt H, Rouault TA, Missirlis F (2013) Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis. J Biol Inorg Chem 18:441–449. https://doi.org/10.1007/s00775-013-0988-2 Schilke B, Williams B, Knieszner H et al (2006) Evolution of mitochondrial chaperones utilized in Fe–S cluster biogenesis. Curr Biol 16:1660–1665. https://doi.org/10.1016/j.cub.2006.06.069 Maio N, Singh A, Uhrigshardt H et al (2014) Cochaperone binding to LYR motifs confers specificity of iron sulfur cluster delivery. Cell Metab 19:445–457. https://doi.org/10.1016/j.cmet.2014.01.015 Bridwell-Rabb J, Iannuzzi C, Pastore A, Barondeau DP (2012) Effector role reversal during evolution: the case of Frataxin in Fe–S cluster biosynthesis. Biochemistry 51:2506–2514. https://doi.org/10.1021/bi201628j Bridwell-Rabb J, Fox NG, Tsai C-L et al (2014) Human Frataxin activates Fe–S cluster biosynthesis by facilitating sulfur transfer chemistry. Biochemistry 53:4904–4913. https://doi.org/10.1021/bi500532e Schmucker S, Martelli A, Colin F et al (2011) Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron–sulfur assembly complex. PLoS One 6:e16199. https://doi.org/10.1371/journal.pone.0016199 Cai K, Frederick RO, Kim JH et al (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 288:28755–28770. https://doi.org/10.1074/jbc.M113.482042 Banci L, Brancaccio D, Ciofi-Baffoni S et al (2014) [2Fe–2S] cluster transfer in iron–sulfur protein biogenesis. Proc Natl Acad Sci USA 111:6203–6208. https://doi.org/10.1073/pnas.1400102111 Camaschella C, Campanella A, De Falco L et al (2007) The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood 110:1353–1358. https://doi.org/10.1182/blood-2007-02-072520 Uzarska MA, Dutkiewicz R, Freibert S-A et al (2013) The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation. Mol Biol Cell 24:1830–1841. https://doi.org/10.1091/mbc.E12-09-0644 Dutkiewicz R, Schilke B, Knieszner H et al (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. https://doi.org/10.1074/jbc.M303527200 Rodríguez-Manzaneque MT, Tamarit J, Bellí G et al (2002) Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol Biol Cell 13:1109–1121. https://doi.org/10.1091/mbc.01-10-0517 Kim K-D, Chung W-H, Kim H-J et al (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. https://doi.org/10.1016/j.bbrc.2010.01.051 Vilella F, Alves R, Rodríguez-Manzaneque MT et al (2004) Evolution and cellular function of monothiol glutaredoxins: involvement in iron–sulphur cluster assembly. Comp Funct Genomics 5:328–341. https://doi.org/10.1002/cfg.406 Sheftel AD, Wilbrecht C, Stehling O et al (2012) The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe–4S] protein maturation. Mol Biol Cell 23:1157–1166. https://doi.org/10.1091/mbc.E11-09-0772 Alaimo JT, Besse A, Alston CL et al (2018) Loss-of-function mutations in ISCA2 disrupt 4Fe–4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion. Hum Mutat 39:537–549. https://doi.org/10.1002/humu.23396 Brancaccio D, Gallo A, Mikolajczyk M et al (2014) Formation of [4Fe–4S] clusters in the mitochondrial iron–sulfur cluster assembly machinery. J Am Chem Soc 136:16240–16250. https://doi.org/10.1021/ja507822j Mühlenhoff U, Gerl MJ, Flauger B et al (2007) 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. https://doi.org/10.1128/EC.00191-06 Mühlenhoff U, Richter N, Pines O et al (2011) Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe–4S] proteins. J Biol Chem 286:41205–41216. https://doi.org/10.1074/jbc.M111.296152 Kaut A, Lange H, Diekert K et al (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. https://doi.org/10.1074/jbc.M909502199 Gelling C, Dawes IW, Richhardt N et al (2008) Mitochondrial Iba57p is required for Fe/S cluster formation on aconitase and activation of radical SAM enzymes. Mol Cell Biol 28:1851–1861. https://doi.org/10.1128/MCB.01963-07 Sánchez LA, Gomez-Gallardo M, Díaz-Pérez AL et al (2018) Iba57p participates in maturation of a [2Fe–2S]-cluster Rieske protein and in formation of supercomplexes III/IV of Saccharomyces cerevisiae electron transport chain. Mitochondrion. https://doi.org/10.1016/j.mito.2018.01.003 Braymer JJ, Lill R (2017) Iron–sulfur cluster biogenesis and trafficking in mitochondria. J Biol Chem 292:12754–12763. https://doi.org/10.1074/jbc.R117.787101 Sheftel AD, Stehling O, Pierik AJ et al (2009) Human Ind1, an iron–sulfur cluster assembly factor for respiratory complex I. Mol Cell Biol 29:6059–6073. https://doi.org/10.1128/MCB.00817-09 Bych K, Kerscher S, Netz DJA et al (2008) The iron–sulphur protein Ind1 is required for effective complex I assembly. EMBO J 27:1736–1746. https://doi.org/10.1038/emboj.2008.98 Tong W-H, Jameson GNL, 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 USA 100:9762–9767. https://doi.org/10.1073/pnas.1732541100 Léon S, Touraine B, Ribot C et al (2003) Iron–sulphur cluster assembly in plants: distinct NFU proteins in mitochondria and plastids from Arabidopsis thaliana. Biochem J 371:823–830. https://doi.org/10.1042/BJ20021946 Melber A, Na U, Vashisht A et al (2016) Role of Nfu1 and Bol3 in iron–sulfur cluster transfer to mitochondrial clients. Elife 5:186. https://doi.org/10.7554/eLife.15991 Gao H, Subramanian S, Couturier J et al (2013) Arabidopsis thaliana Nfu2 accommodates [2Fe–2S] or [4Fe–4S] clusters and is competent for in vitro maturation of chloroplast [2Fe–2S] and [4Fe–4S] cluster-containing proteins. Biochemistry 52:6633–6645. https://doi.org/10.1021/bi4007622 Wachnowsky C, Fidai I, Cowan JA (2016) Iron–sulfur cluster exchange reactions mediated by the human Nfu protein. J Biol Inorg Chem 21:825–836. https://doi.org/10.1007/s00775-016-1381-8 Benoit SL, Holland AA, Johnson MK, Maier RJ (2018) Iron–sulfur protein maturation in Helicobacter pylori: identifying a Nfu-type cluster carrier protein and its iron–sulfur protein targets. Mol Microbiol. https://doi.org/10.1111/mmi.13942 Tonduti D, Dorboz I, Imbard A et al (2015) New spastic paraplegia phenotype associated to mutation of NFU1. Orphanet J Rare Dis 10:13. https://doi.org/10.1186/s13023-015-0237-6 Navarro-Sastre A, Tort F, Stehling O et al (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 89:656–667. https://doi.org/10.1016/j.ajhg.2011.10.005 Cameron JM, Janer A, Levandovskiy V et al (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. https://doi.org/10.1016/j.ajhg.2011.08.011 Uzarska MA, Nasta V, Weiler BD et al (2016) Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron–sulfur proteins. Elife 5:e16673. https://doi.org/10.7554/eLife.16673 Willems P, Wanschers BFJ, Esseling J et al (2013) BOLA1 Is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion. Antioxid Redox Signal 18:129–138. https://doi.org/10.1089/ars.2011.4253 Frey AG, Palenchar DJ, Wildemann JD, Philpott CC (2016) A glutaredoxin BolA complex serves as an iron–sulfur cluster chaperone for the cytosolic cluster assembly machinery. J Biol Chem 291:22344–22356. https://doi.org/10.1074/jbc.M116.744946 Sipos K, Lange H, Fekete Z et al (2002) Maturation of cytosolic iron–sulfur proteins requires glutathione. J Biol Chem 277:26944–26949. https://doi.org/10.1074/jbc.M200677200 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 18:3981–3989. https://doi.org/10.1093/emboj/18.14.3981 Leighton J, Schatz G (1995) An ABC transporter in the mitochondrial inner membrane is required for normal growth of yeast. EMBO J 14:188–195 Balk J, Pierik AJ, Netz DJA et al (2004) The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron–sulphur proteins. EMBO J 23:2105–2115. https://doi.org/10.1038/sj.emboj.7600216 Stehling O, Lill R (2013) The role of mitochondria in cellular iron–sulfur protein biogenesis: mechanisms, connected processes, and diseases. Cold Spring Harb Perspect Biol 5:a011312. https://doi.org/10.1101/cshperspect.a011312 Srinivasan V, Pierik AJ, Lill R (2014) Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1. Science 343:1137–1140. https://doi.org/10.1126/science.1246729 Roy A, Solodovnikova N, Nicholson T et al (2003) A novel eukaryotic factor for cytosolic Fe–S cluster assembly. EMBO J 22:4826–4835. https://doi.org/10.1093/emboj/cdg455 Hausmann A, Aguilar Netz DJ, Balk J et al (2005) The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron–sulfur protein assembly machinery. Proc Natl Acad Sci USA 102:3266–3271. https://doi.org/10.1073/pnas.0406447102 Netz DJA, Pierik AJ, Stümpfig M et al (2007) The Cfd1–Nbp35 complex acts as a scaffold for iron–sulfur protein assembly in the yeast cytosol. Nat Chem Biol 3:278–286. https://doi.org/10.1038/nchembio872 Boyd JM, Drevland RM, Downs DM, Graham DE (2009) Archaeal ApbC/Nbp35 homologs function as iron–sulfur cluster carrier proteins. J Bacteriol 191:1490–1497. https://doi.org/10.1128/JB.01469-08 Netz DJA, Pierik AJ, Stumpfig M et al (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 287:12365–12378. https://doi.org/10.1074/jbc.M111.328914 Stehling O, Netz DJA, Niggemeyer B et al (2008) Human Nbp35 is essential for both cytosolic iron–sulfur protein assembly and iron homeostasis. Mol Cell Biol 28:5517–5528. https://doi.org/10.1128/MCB.00545-08 Bych K, Netz DJA, Vigani G et al (2008) The essential cytosolic iron–sulfur protein Nbp35 acts without Cfd1 partner in the green lineage. J Biol Chem 283:35797–35804. https://doi.org/10.1074/jbc.M807303200 Pyrih J, Pyrihová E, Kolísko M et al (2016) Minimal cytosolic iron–sulfur cluster assembly machinery of Giardia intestinalis is partially associated with mitosomes. Mol Microbiol 102:701–714. https://doi.org/10.1111/mmi.13487 Netz DJA, Stümpfig M, Doré C et al (2010) Tah18 transfers electrons to Dre2 in cytosolic iron–sulfur protein biogenesis. Nat Chem Biol 6:758–765. https://doi.org/10.1038/nchembio.432 Zhang Y, Lyver ER, Nakamaru-Ogiso E et al (2008) Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis. Mol Cell Biol 28:5569–5582. https://doi.org/10.1128/MCB.00642-08 Peleh V, Riemer J, Dancis A, Herrmann JM (2014) Protein oxidation in the intermembrane space of mitochondria is substrate-specific rather than general. Microb Cell 1:81–93. https://doi.org/10.15698/mic2014.01.130 Banci L, Bertini I, Ciofi-Baffoni S et al (2011) Anamorsin is a [2Fe–2S] cluster-containing substrate of the Mia40-dependent mitochondrial protein trapping machinery. Chem Biol 18:794–804. https://doi.org/10.1016/j.chembiol.2011.03.015 Netz DJA, Genau HM, Weiler BD et al (2016) The conserved protein Dre2 uses essential [2Fe–2S] and [4Fe–4S] clusters for its function in cytosolic iron–sulfur protein assembly. Biochem J 473:2073–2085. https://doi.org/10.1042/BCJ20160416 Banci L, Ciofi-Baffoni S, Gajda K et al (2015) N-terminal domains mediate [2Fe–2S] cluster transfer from glutaredoxin-3 to anamorsin. Nat Chem Biol 11:772–778. https://doi.org/10.1038/nchembio.1892 Balk J, Aguilar Netz DJ, Tepper K et al (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. https://doi.org/10.1128/MCB.25.24.10833-10841.2005 Stehling O, Vashisht AA, Mascarenhas J et al (2012) MMS19 assembles iron–sulfur proteins required for DNA metabolism and genomic integrity. Science 337:195–199. https://doi.org/10.1126/science.1219723 Gari K, Ortiz AML, Borel V et al (2012) MMS19 links cytoplasmic iron–sulfur cluster assembly to DNA metabolism. Science 337:243–245. https://doi.org/10.1126/science.1219664 Odermatt DC, Gari K (2017) The CIA targeting complex is highly regulated and provides two distinct binding sites for client iron–sulfur proteins. Cell Rep 18:1434–1443. https://doi.org/10.1016/j.celrep.2017.01.037 Srinivasan V, Netz DJA, Webert H et al (2007) Structure of the yeast WD40 domain protein Cia1, a component acting late in iron–sulfur protein biogenesis. Structure 15:1246–1257. https://doi.org/10.1016/j.str.2007.08.009 Prakash L, Prakash S (1979) Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14 and MMS19. Mol Gen Genet 176:351–359. https://doi.org/10.1007/BF00333097 Li F, Martienssen R, Cande WZ (2011) Coordination of DNA replication and histone modification by the Rik1–Dos2 complex. Nature 475:244–248. https://doi.org/10.1038/nature10161 Eisenstein RS (2000) Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu Rev Nutr 20:627–662. https://doi.org/10.1146/annurev.nutr.20.1.627 Mühlenhoff U, Molik S, Godoy JR et al (2010) Cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron–sulfur cluster. Cell Metab 12:373–385. https://doi.org/10.1016/j.cmet.2010.08.001 Yarunin A, Panse VG, Petfalski E et al (2005) Functional link between ribosome formation and biogenesis of iron–sulfur proteins. EMBO J 24:580–588. https://doi.org/10.1038/sj.emboj.7600540 Van Ho A, Ward DM, Kaplan J (2002) Transition metal transport in yeast. Annu Rev Microbiol 56:237–261. https://doi.org/10.1146/annurev.micro.56.012302.160847 Ojeda L, Keller G, Mühlenhoff U et al (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. https://doi.org/10.1074/jbc.M602165200 Pujol-Carrion N, Bellí G, Herrero E et al (2006) Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae. J Cell Sci 119:4554–4564. https://doi.org/10.1242/jcs.03229 Chen OS, Crisp RJ, Valachovic M et al (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. https://doi.org/10.1074/jbc.M403209200 Rutherford JC, Ojeda L, Balk J et al (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. https://doi.org/10.1074/jbc.M413731200 Kumánovics A, Chen OS, Li L et al (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. https://doi.org/10.1074/jbc.M801160200 Li Y (1995) Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. Proc Natl Acad Sci USA 92:10864–10868. https://doi.org/10.1073/pnas.1714341115 Aldea M, Hernández-Chico C, la Campa de AG et al (1988) Identification, cloning, and expression of bolA, an ftsZ-dependent morphogene of Escherichia coli. J Bacteriol 170:5169–5176. https://doi.org/10.1128/jb.170.11.5169-5176.1988 Li H, Mapolelo DT, Dingra NN et al (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. https://doi.org/10.1074/jbc.M110.184176 Haunhorst P, Berndt C, Eitner S et al (2010) Characterization of the human monothiol glutaredoxin 3 (PICOT) as iron–sulfur protein. Biochem Biophys Res Commun 394:372–376. https://doi.org/10.1016/j.bbrc.2010.03.016 Hampl V, Hug L, Leigh JW et al (2009) Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic “supergroups”. Proc Natl Acad Sci USA 106:3859–3864. https://doi.org/10.1073/pnas.0807880106 Derelle R, Torruella G, Klimeš V et al (2015) Bacterial proteins pinpoint a single eukaryotic root. Proc Natl Acad Sci USA 112:E693–E699. https://doi.org/10.1073/pnas.1420657112 Lukeš J, Basu S (2015) Fe/S protein biogenesis in trypanosomes—a review. Biochim Biophys Acta 1853:1481–1492. https://doi.org/10.1016/j.bbamcr.2014.08.015 Hannaert V, Bringaud F, Opperdoes FR, Michels PA (2003) Evolution of energy metabolism and its compartmentation in Kinetoplastida. Kinetoplastid Biol Dis 2:11. https://doi.org/10.1186/1475-9292-2-11 Basu S, Horáková E, Lukeš J (2016) Iron-associated biology of Trypanosoma brucei. BBA Gen Subjects 1860:363–370. https://doi.org/10.1016/j.bbagen.2015.10.027 Smíd O, Horáková E, Vilímová V et al (2006) Knock-downs of iron–sulfur cluster assembly proteins IscS and IscU down-regulate the active mitochondrion of procyclic Trypanosoma brucei. J Biol Chem 281:28679–28686. https://doi.org/10.1074/jbc.M513781200 Paris Z, Changmai P, Rubio MAT et al (2010) The Fe/S cluster assembly protein Isd11 is essential for tRNA thiolation in Trypanosoma brucei. J Biol Chem 285:22394–22402. https://doi.org/10.1074/jbc.M109.083774 Changmai P, Horáková E, Long S et al (2013) Both human ferredoxins equally efficiently rescue ferredoxin deficiency in Trypanosoma brucei. Mol Microbiol 89:135–151. https://doi.org/10.1111/mmi.12264 Comini MA, Rettig J, Dirdjaja N et al (2008) Monothiol glutaredoxin-1 is an essential iron–sulfur protein in the mitochondrion of african trypanosomes. J Biol Chem 283:27785–27798. https://doi.org/10.1074/jbc.M802010200 Long S, Jirků M, Ayala FJ, Lukeš J (2008) Mitochondrial localization of human frataxin is necessary but processing is not for rescuing frataxin deficiency in Trypanosoma brucei. Proc Natl Acad Sci USA 105:13468–13473. https://doi.org/10.1073/pnas.0806762105 Long S, Changmai P, Tsaousis AD et al (2011) Stage-specific requirement for Isa1 and Isa2 proteins in the mitochondrion of Trypanosoma brucei and heterologous rescue by human and Blastocystis orthologues. Mol Microbiol 81:1403–1418. https://doi.org/10.1111/j.1365-2958.2011.07769.x Horáková E, Changmai P, Paris Z et al (2015) Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe–S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei. FEBS J 282:4157–4175. https://doi.org/10.1111/febs.13411 Basu S, Leonard JC, Desai N et al (2013) Divergence of Erv1-associated mitochondrial import and export pathways in trypanosomes and anaerobic protists. Eukaryot Cell 12:343–355. https://doi.org/10.1128/EC.00304-12 Haindrich AC, Boudová M, Vancová M et al (2017) The intermembrane space protein Erv1 of Trypanosoma brucei is essential for mitochondrial Fe–S cluster assembly and operates alone. Mol Biochem Parasitol 214:47–51. https://doi.org/10.1016/j.molbiopara.2017.03.009 Kovářová J, Horáková E, Changmai P et al (2014) Mitochondrial and nucleolar localization of cysteine desulfurase Nfs and the scaffold protein Isu in Trypanosoma brucei. Eukaryot Cell 13:353–362. https://doi.org/10.1128/EC.00235-13 Benz C, Kovářová J, Králová-Hromadová I et al (2016) Roles of the Nfu Fe–S targeting factors in the trypanosome mitochondrion. Int J Parasitol 46:641–651. https://doi.org/10.1016/j.ijpara.2016.04.006 Saunders EC, Ng WW, Kloehn J et al (2014) Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism. PLoS Pathog 10:e1003888. https://doi.org/10.1371/journal.ppat.1003888 Pratap Singh K, Zaidi A, Anwar S et al (2014) Reactive oxygen species regulates expression of iron–sulfur cluster assembly protein IscS of Leishmania donovani. Free Radic Biol Med 75:195–209. https://doi.org/10.1016/j.freeradbiomed.2014.07.017 Filser M, Comini MA, Molina-Navarro MM et al (2008) Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1. Biol Chem 389:21–32. https://doi.org/10.1515/BC.2007.147 Comini MA, Krauth-Siegel RL, Bellanda M (2013) Mono- and dithiol glutaredoxins in the trypanothione-based redox metabolism of pathogenic trypanosomes. Antioxid Redox Signal 19:708–722. https://doi.org/10.1089/ars.2012.4932 Manta B, Pavan C, Sturlese M et al (2013) Iron–sulfur cluster binding by mitochondrial monothiol glutaredoxin-1 of Trypanosoma brucei: molecular basis of iron–sulfur cluster coordination and relevance for parasite infectivity. Antioxid Redox Signal 19:665–682. https://doi.org/10.1089/ars.2012.4859 Pánek T, Čepička I (2012) Diversity of heterolobosea. Genet Divers Microorg. https://doi.org/10.5772/35333 De Jonckheere JF, Baumgartner M, Opperdoes FR, Stetter KO (2009) Marinamoeba thermophila, a new marine heterolobosean amoeba growing at 50 °C. Eur J Protistol 45:231–236. https://doi.org/10.1016/j.ejop.2009.01.001 Park JS, Simpson AGB, Lee WJ, Cho BC (2007) Ultrastructure and phylogenetic placement within Heterolobosea of the previously unclassified, extremely halophilic heterotrophic flagellate Pleurostomum flabellatum (Ruinen 1938). Ann Anat 158:397–413. https://doi.org/10.1016/j.protis.2007.03.004 De Jonckheere JF (2006) Isolation and molecular identification of free-living amoebae of the genus Naegleria from Arctic and sub-Antarctic regions. Eur J Protistol 42:115–123. https://doi.org/10.1016/j.ejop.2006.02.001 Park JS, Simpson AGB (2015) Diversity of heterotrophic protists from extremely hypersaline habitats. Ann Anat 166:422–437. https://doi.org/10.1016/j.protis.2015.06.001 Geisen S, Bonkowski M, Zhang J, De Jonckheere JF (2015) Heterogeneity in the genus Allovahlkampfia and the description of the new genus Parafumarolamoeba (Vahlkampfiidae; Heterolobosea). Eur J Protistol 51:335–349. https://doi.org/10.1016/j.ejop.2015.05.003 Baumgartner M, Eberhardt S, De Jonckheere JF, Stetter KO (2009) Tetramitus thermacidophilus n. sp., an amoeboflagellate from acidic hot springs. J Eukaryot Microbiol 56:201–206. https://doi.org/10.1111/j.1550-7408.2009.00390.x Visvesvara GS, Sriram R, Qvarnstrom Y et al (2009) Paravahlkampfia francinae n. sp. masquerading as an agent of primary amoebic meningoencephalitis. J Eukaryot Microbiol 56:357–366. https://doi.org/10.1111/j.1550-7408.2009.00410.x O’Kelly CJ, Silberman JD, Amaral Zettler LA et al (2003) Monopylocystis visvesvarai n. gen., n. sp. and Sawyeria marylandensis n. gen., n. sp.: two new amitochondrial heterolobosean amoebae from anoxic environments. Ann Anat 154:281–290. https://doi.org/10.1078/143446103322166563 Barbera MJ, Ruiz-Trillo I, Tufts JYA et al (2010) Sawyeria marylandensis (Heterolobosea) has a hydrogenosome with novel metabolic properties. Eukaryot Cell 9:1913–1924. https://doi.org/10.1128/EC.00122-10 Broers CA, Stumm CK, Vogels GD, Brugerolle G (1990) Psalteriomonas lanterna gen. nov., sp. nov., a free-living amoeboflagellate isolated from freshwater anaerobic sediments. Eur J Protistol 25:369–380. https://doi.org/10.1016/S0932-4739(11)80130-6 de Graaf RM, Duarte I, van Alen TA et al (2009) The hydrogenosomes of Psalteriomonas lanterna. BMC Evol Biol 9:287. https://doi.org/10.1186/1471-2148-9-287 Pánek T, Silberman JD, Yubuki N et al (2012) Diversity, evolution and molecular systematics of the Psalteriomonadidae, the main lineage of anaerobic/microaerophilic heteroloboseans (excavata: discoba). Protist 163:807–831. https://doi.org/10.1016/j.protis.2011.11.002 Pánek T, Simpson AGB, Hampl V, Čepička I (2014) Creneis carolina gen. et sp. nov. (Heterolobosea), a novel marine anaerobic protist with strikingly derived morphology and life cycle. Ann Anat. https://doi.org/10.1016/j.protis.2014.05.005 Smirnov AV, Fenchel T (1996) Vahlkampfia anaerobica n. sp. and Vannella peregrinia n. sp. (Rhizopoda)—anaerobic amoebae from a marine sediment. Arch Protistenkd 147:189–198. https://doi.org/10.1016/S0003-9365(96)80033-9 Lang BF, Burger G, O’Kelly CJ et al (1997) An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387:493–497. https://doi.org/10.1038/387493a0 Lara E, Chatzinotas A, Simpson AGB (2006) Andalucia (n. gen.)-the deepest branch within jakobids (Jakobida; Excavata), based on morphological and molecular study of a new flagellate from soil. J Eukaryot Microbiol 53:112–120. https://doi.org/10.1111/j.1550-7408.2005.00081.x He D, Fu C-J, Baldauf SL (2015) Multiple origins of eukaryotic cox15 suggest horizontal gene transfer from bacteria to jakobid mitochondrial DNA. Mol Biol Evol 33:122–133. https://doi.org/10.1093/molbev/msv201 Burger G, Gray MW, Forget L, Lang BF (2013) Strikingly bacteria-like and gene-rich mitochondrial genomes throughout jakobid protists. Genome Biol Evol 5:418–438. https://doi.org/10.1093/gbe/evt008 Leger MM, Eme L, Hug LA, Roger AJ (2016) Novel hydrogenosomes in the microaerophilic jakobid Stygiella incarcerata. Mol Biol Evol MSW. https://doi.org/10.1093/molbev/msw103 Dolezal P, Dagley MJ, Kono M et al (2010) The essentials of protein import in the degenerate mitochondrion of Entamoeba histolytica. PLoS Pathog 6:e1000812. https://doi.org/10.1371/journal.ppat.1000812 Rada P, Makki AR, Zimorski V et al (2015) N-terminal presequence-independent import of phosphofructokinase into hydrogenosomes of Trichomonas vaginalis. Eukaryot Cell 14:1264–1275. https://doi.org/10.1128/EC.00104-15 Garg S, Stölting J, Zimorski V et al (2015) Conservation of transit peptide-independent protein import into the mitochondrial and hydrogenosomal matrix. Genome Biol Evol 7:2716–2726. https://doi.org/10.1093/gbe/evv175 Xu F, Jerlström-Hultqvist J, Einarsson E et al (2014) The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments. PLoS Genet 10:e1004053. https://doi.org/10.1371/journal.pgen.1004053 Zhang Q, Táborský P, Silberman JD et al (2015) Marine isolates of Trimastix marina form a plesiomorphic deep-branching lineage within Preaxostyla, separate from other known trimastigids (Paratrimastix n. gen.). Protist 166:468–491. https://doi.org/10.1016/j.protis.2015.07.003 Tovar J, León-Avila G, Sánchez LB et al (2003) Mitochondrial remnant organelles of Giardia function in iron–sulphur protein maturation. Nature 426:172–176. https://doi.org/10.1038/nature01945 Rada P, Smid O, Sutak R et al (2009) The monothiol single-domain glutaredoxin is conserved in the highly reduced mitochondria of Giardia intestinalis. Eukaryot Cell 8:1584–1591. https://doi.org/10.1128/EC.00181-09 Dolezal P, Šmid O, Rada P et al (2005) Giardia mitosomes and trichomonad hydrogenosomes share a common mode of protein targeting. Proc Natl Acad Sci USA 102:10924–10929. https://doi.org/10.1073/pnas.0500349102 Jedelský PL, Dolezal P, Rada P et al (2011) The minimal proteome in the reduced mitochondrion of the parasitic protist Giardia intestinalis. PLoS One 6:e17285. https://doi.org/10.1371/journal.pone.0017285 Rout S, Zumthor JP, Schraner EM et al (2016) An interactome-centered protein discovery approach reveals novel components involved in mitosome function and homeostasis in Giardia lamblia. PLoS Pathog 12:e1006036. https://doi.org/10.1371/journal.ppat.1006036 Regoes A, Zourmpanou D, León-Avila G et al (2005) Protein import, replication, and inheritance of a vestigial mitochondrion. J Biol Chem 280:30557–30563. https://doi.org/10.1074/jbc.M500787200 Jerlström-Hultqvist J, Einarsson E, Xu F et al (2013) Hydrogenosomes in the diplomonad Spironucleus salmonicida. Nat Commun 4:2493. https://doi.org/10.1038/ncomms3493 Millet COM, Cable J, Lloyd D (2010) The diplomonad fish parasite Spironucleus vortens produces hydrogen. J Eukaryot Microbiol 57:400–404. https://doi.org/10.1111/j.1550-7408.2010.00499.x Horváthová L, Šafaříková L, Basler M et al (2012) Transcriptomic identification of iron-regulated and iron-independent gene copies within the heavily duplicated Trichomonas vaginalis genome. Genome Biol Evol 4:1017–1029. https://doi.org/10.1093/gbe/evs078 Beltrán NC, Horváthová L, Jedelský PL et al (2013) Iron-induced changes in the proteome of Trichomonas vaginalis hydrogenosomes. PLoS One 8:e65148. https://doi.org/10.1371/journal.pone.0065148 Gorrell TE (1985) Effect of culture medium iron content on the biochemical composition and metabolism of Trichomonas vaginalis. J Bacteriol 161:1228–1230 Figueroa-Angulo E, Calla-Choque J, Mancilla-Olea M, Arroyo R (2015) RNA-binding proteins in Trichomonas vaginalis: atypical multifunctional proteins. Biomolecules 5:3354–3395. https://doi.org/10.3390/biom5043354 Clemens DL, Johnson PJ (2000) Failure to detect DNA in hydrogenosomes of Trichomonas vaginalis by nick translation and immunomicroscopy. Mol Biochem Parasitol 106:307–313. https://doi.org/10.1016/S0166-6851(99)00220-0 Dolezal P, Dancis A, Lesuisse E et al (2007) Frataxin, a conserved mitochondrial protein, in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell 6:1431–1438. https://doi.org/10.1128/EC.00027-07 Sutak R, Dolezal P, Fiumera HL et al (2004) Mitochondrial-type assembly of FeS centers in the hydrogenosomes of the amitochondriate eukaryote Trichomonas vaginalis. Proc Natl Acad Sci USA 101:10368–10373. https://doi.org/10.1073/pnas.0401319101 Schneider RE, Brown MT, Shiflett AM et al (2011) The Trichomonas vaginalis hydrogenosome proteome is highly reduced relative to mitochondria, yet complex compared with mitosomes. Int J Parasitol 41:1421–1434. https://doi.org/10.1016/j.ijpara.2011.10.001 Smutná T, Pilarová K, Tarábek J et al (2014) Novel functions of an iron–sulfur flavoprotein from Trichomonas vaginalis hydrogenosomes. Antimicrob Agents Chemother 58:3224–3232. https://doi.org/10.1128/AAC.02320-13 Ferry JG (1997) Enzymology of the fermentation of acetate to methane by Methanosarcina thermophila. BioFactors 6:25–35 Zhao T, Cruz F, Ferry JG (2001) Iron–sulfur flavoprotein (Isf) from Methanosarcina thermophila is the prototype of a widely distributed family. J Bacteriol 183:6225–6233. https://doi.org/10.1128/JB.183.21.6225-6233.2001 Hampl V, Silberman JD, Stechmann A et al (2008) Genetic evidence for a mitochondriate ancestry in the “amitochondriate” flagellate Trimastix pyriformis. PLoS One 3:e1383. https://doi.org/10.1371/journal.pone.0001383 Kurihara T, Mihara H, Kato S-I et al (2003) Assembly of iron–sulfur clusters mediated by cysteine desulfurases, IscS, CsdB and CSD, from Escherichia coli. Biochim Biophys Acta 1647:303–309. https://doi.org/10.1016/S1570-9639(03)00078-5 Loiseau L, Gerez C, Bekker M et al (2007) ErpA, an iron sulfur (Fe S) protein of the A-type essential for respiratory metabolism in Escherichia coli. Proc Natl Acad Sci USA 104:13626–13631. https://doi.org/10.1073/pnas.0705829104 Lu J, Yang J, Tan G, Ding H (2008) Complementary roles of SufA and IscA in the biogenesis of iron–sulfur clusters in Escherichia coli. Biochem J 409:535–543. https://doi.org/10.1042/BJ20071166 Jensen LT, Culotta VC (2000) Role of Saccharomyces cerevisiae ISA1 and ISA2 in iron homeostasis. Mol Cell Biol 20:3918–3927 Johnson DC, Unciuleac MC, Dean DR (2006) Controlled expression and functional analysis of iron–sulfur cluster biosynthetic components within Azotobacter vinelandii. J Bacteriol 188:7551–7561. https://doi.org/10.1128/JB.00596-06 Boyd ES, Thomas KM, Dai Y et al (2014) Interplay between oxygen and Fe–S cluster biogenesis: insights from the Suf pathway. Biochemistry 53:5834–5847. https://doi.org/10.1021/bi500488r Riboldi GP, Larson TJ, Frazzon J (2011) Enterococcus faecalis sufCDSUB complements Escherichia coli sufABCDSE. FEMS Microbiol Lett 320:15–24. https://doi.org/10.1111/j.1574-6968.2011.02284.x Riboldi GP, Verli H, Frazzon J (2009) Structural studies of the Enterococcus faecalis SufU [Fe–S] cluster protein. BMC Biochem 10:3–10. https://doi.org/10.1186/1471-2091-10-3 Xu XM, Møller SG (2004) AtNAP7 is a plastidic SufC-like ATP-binding cassette/ATPase essential for Arabidopsis embryogenesis. Proc Natl Acad Sci USA 101:9143–9148. https://doi.org/10.1073/pnas.0400799101 Xu XM, Adams S, Chua N-H, Møller SG (2005) AtNAP1 represents an atypical SufB protein in Arabidopsis plastids. J Biol Chem 280:6648–6654. https://doi.org/10.1074/jbc.M413082200 Møller SG, Kunkel T, Chua NH (2001) A plastidic ABC protein involved in intercompartmental communication of light signaling. Genes Dev 15:90–103. https://doi.org/10.1101/gad.850101 Romsang A, Duang-Nkern J, Leesukon P et al (2014) The iron–sulphur cluster biosynthesis regulator IscR contributes to iron homeostasis and resistance to oxidants in Pseudomonas aeruginosa. PLoS One 9:e86763. https://doi.org/10.1371/journal.pone.0086763 van der Gulik PTS, Hoff WD, Speijer D (2017) In defence of the three-domains of life paradigm. BMC Evol Biol 17:218. https://doi.org/10.1186/s12862-017-1059-z Embley TM (2006) Multiple secondary origins of the anaerobic lifestyle in eukaryotes. Philos Trans R Soc Lond B Biol Sci 361:1055–1067. https://doi.org/10.1098/rstb.2006.1844