{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:34:37Z","timestamp":1789554877370,"version":"build-2803163510"},"reference-count":73,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T00:00:00Z","timestamp":1441929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content> transporter mitochondrial 1 (Atm1) and multidrug resistance\u2010like 1 (Mdl) are mitochondrial <jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content> transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron\u2010sulfur (Fe\u2010S) cluster maturation in the cytosol, the function of Mdl remains elusive. In <jats:italic>Trypanosoma\u00a0brucei<\/jats:italic>, we identified one homolog of each of these genes, <jats:italic>Tb<\/jats:italic>Atm and <jats:italic>Tb<\/jats:italic>Mdl, which were downregulated either separately or simultaneously using <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> interference. Individual depletion of <jats:italic>Tb<\/jats:italic>Atm and <jats:italic>Tb<\/jats:italic>Mdl led to limited growth defects. In cells downregulated for <jats:italic>Tb<\/jats:italic>Atm, the enzymatic activities of the Fe\u2010S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of <jats:italic>Tb<\/jats:italic>Mdl did not cause any change in activities of the Fe\u2010S proteins. Unexpectedly, the simultaneous downregulation of <jats:italic>Tb<\/jats:italic>Atm and <jats:italic>Tb<\/jats:italic>Mdl did not result in any growth defect, nor were the Fe\u2010S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, <jats:italic>Tb<\/jats:italic>Atm and <jats:italic>Tb<\/jats:italic>Mdl were able to partially restore the growth of the <jats:italic>Saccharomyces\u00a0cerevisiae<\/jats:italic> \u0394<jats:italic>atm1<\/jats:italic> and \u0394<jats:italic>mdl2<\/jats:italic> null mutants, respectively. Because <jats:italic>T.\u00a0brucei<\/jats:italic> completely lost the heme <jats:italic>b<\/jats:italic> biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, <jats:italic>Tb<\/jats:italic>Mdl is a candidate for mitochondrial import of heme <jats:italic>b<\/jats:italic>, which was markedly decreased in both <jats:italic>Tb<\/jats:italic>Mdl and <jats:italic>Tb<\/jats:italic>Atm\u00a0+\u00a0<jats:italic>Tb<\/jats:italic>Mdl knockdowns. Moreover, the levels of heme <jats:italic>a<\/jats:italic> were strongly decreased in the same knockdowns, suggesting that <jats:italic>Tb<\/jats:italic>Mdl plays a key role in heme <jats:italic>a<\/jats:italic> biosynthesis, thus affecting the overall heme homeostasis in <jats:italic>T.\u00a0brucei<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/febs.13411","type":"journal-article","created":{"date-parts":[[2015,8,16]],"date-time":"2015-08-16T12:29:20Z","timestamp":1439728160000},"page":"4157-4175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe\u2010S cluster assembly but not heme import into the mitochondrion of <i>Trypanosoma\u00a0brucei<\/i>"],"prefix":"10.1111","volume":"282","author":[{"given":"Eva","family":"Hor\u00e1kov\u00e1","sequence":"first","affiliation":[{"name":"Biology Centre Institute of Parasitology Czech Academy of Sciences \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piya","family":"Changmai","sequence":"additional","affiliation":[{"name":"Biology Centre Institute of Parasitology Czech Academy of Sciences \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"},{"name":"Faculty of Sciences University of South Bohemia \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zden\u011bk","family":"Paris","sequence":"additional","affiliation":[{"name":"Biology Centre Institute of Parasitology Czech Academy of Sciences \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Salmon","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis Centro de Ci\u00eancias e da Saude Federal University of Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Luke\u0161","sequence":"additional","affiliation":[{"name":"Biology Centre Institute of Parasitology Czech Academy of Sciences \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"},{"name":"Faculty of Sciences University of South Bohemia \u010cesk\u00e9 Bud\u011bjovice (Budweis) Czech Republic"},{"name":"Canadian Institute for Advanced Research Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08301"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.721"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.09.015"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2754"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi010544t"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja027967i"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi800366d"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2007.00296.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1579"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00191-06"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07769.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-09-0772"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.02.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00112-06"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.05.051"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.14.3981"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.109.068478"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb06989.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi901110n"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200677200"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.105"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1212"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.3256"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-041632"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702383200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.109.143651"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246729"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.553438"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246489"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056957"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609899200"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00666-1"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904519106"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259614"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301552"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2273"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2004.09.002"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.11.007"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2010.02109.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12264"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800477"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-09-0841"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00304-12"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2745"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601377200"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01321-06"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003647"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00865-13"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.015"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156296"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.420745"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.13.1.89"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.195"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201089109"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.052705.162653"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.029421"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(98)00184-1"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2003.062"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(91)90170-B"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf436"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msp259"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu033"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405933200"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.888808"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506133102"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513781200"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.07.005"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1970.tb00817.x"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(80)90055-8"},{"key":"e_1_2_8_72_1","first-page":"59","volume-title":"Methods in Yeast Genetics: A Cold Spring Harbor Laboratory Course Manual","author":"Amberg DC","year":"2005"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.13.2519"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00410a048"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.13411","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.13411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T21:27:43Z","timestamp":1696368463000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.13411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,11]]},"references-count":73,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/febs.13411"],"URL":"https:\/\/doi.org\/10.1111\/febs.13411","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,11]]},"assertion":[{"value":"2015-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}