{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:34:30Z","timestamp":1791333270259,"version":"4.3.1"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T00:00:00Z","timestamp":1447891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Basic Research Program of China, MoST 973 program","award":["2012CB934000"],"award-info":[{"award-number":["2012CB934000"]}]},{"name":"National Distinguished Youth Scholar Grant of China","award":["31325010"],"award-info":[{"award-number":["31325010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Glutaredoxin 5 (GLRX5) is a 156 amino acid mitochondrial protein that plays an essential role in mitochondrial iron\u2010sulfur cluster transfer. Mutations in this protein were reported to result in sideroblastic anemia and variant nonketotic hyperglycinemia in human. Recently, we have characterized a Chinese congenital sideroblastic anemia patient who has two compound heterozygous missense mutations (c. 301 A&gt;C and c. 443 T&gt;C) in his <jats:italic>GLRX5<\/jats:italic> gene. Herein, we developed a GLRX5 knockout K562 cell line and studied the biochemical functions of the identified pathogenic mutations and other conserved amino acids with predicted essential functions. We observed that the K101Q mutation (due to c. 301 A&gt;C mutation) may prevent the binding of [Fe\u2010S] to GLRX5 protein, while L148S (due to c. 443 T&gt;C mutation) may interfere with [Fe\u2010S] transfer from GLRX5 to iron regulatory protein 1 (IRP1), mitochondrial aconitase (m\u2010aconitase) and ferrochelatase. We also demonstrated that L148S is functionally complementary to the K51del mutant with respect to Fe\/S\u2010ferrochelatase, Fe\/S\u2010IRP1, Fe\/S\u2010succinate dehydrogenase, and Fe\/S\u2010m\u2010aconitase biosynthesis and lipoylation of pyruvate dehydrogenase complex and \u03b1\u2010ketoglutarate dehydrogenase complex. Furthermore, we demonstrated that the mutations of highly conserved amino acid residues in GLRX5 protein can have different effects on downstream Fe\/S proteins. Collectively, our current work demonstrates that GLRX5 protein is multifunctional in [Fe\u2010S] protein synthesis and maturation and defects of the different amino acids of the protein will lead to distinct effects on downstream Fe\/S biosynthesis. J. Cell. Biochem. 117: 207\u2013217, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25267","type":"journal-article","created":{"date-parts":[[2015,6,22]],"date-time":"2015-06-22T22:44:08Z","timestamp":1435013048000},"page":"207-217","source":"Crossref","is-referenced-by-count":44,"title":["Functional Analysis of <i>GLRX5<\/i> Mutants Reveals Distinct Functionalities of GLRX5 Protein"],"prefix":"10.1002","volume":"117","author":[{"given":"Gang","family":"Liu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology, No.11 Zhongguancun Beiyitiao Beijing 100190 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwei","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology, No.11 Zhongguancun Beiyitiao Beijing 100190 China"},{"name":"Laboratory of Molecular Iron Metabolism College of Life Science Hebei Normal University Shijiazhuang 050024 Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Iron Metabolism Laboratory QIMR Berghofer Medical Research Institute Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Camaschella","sequence":"additional","affiliation":[{"name":"Vita\u2010Salute University and IRCCS San Raffaele Scientific Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhong","family":"Chang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Iron Metabolism College of Life Science Hebei Normal University Shijiazhuang 050024 Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjun","family":"Nie","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology, No.11 Zhongguancun Beiyitiao Beijing 100190 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt328"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-072520"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi035386f"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243105"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)69006-5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00249a034"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.12217"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101286"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.84.246"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08301"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.05.009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-598508"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.1.1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.143"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2008.05.008"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-09-0644"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03887"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40372"}],"container-title":["Journal 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