Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia
Abstract
The sideroblastic anemias are a heterogeneous group of congenital and acquired hematological disorders whose morphological hallmark is the presence of ringed sideroblasts--bone marrow erythroid precursors containing pathologic iron deposits within mitochondria. Here, by positional cloning, we define a previously unknown form of autosomal recessive nonsyndromic congenital sideroblastic anemia, associated with mutations in the gene encoding the erythroid specific mitochondrial carrier family protein SLC25A38, and demonstrate that SLC25A38 is important for the biosynthesis of heme in eukaryotes.
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Hereditary sideroblastic anemias are usually due to heme deficiency: X-linked sideroblastic anemia is caused by mutations in ALAS2, the first, rate-limiting enzyme of heme biosynthesis, while recessive forms are associated with mutations of mitochondria glycine importer solute carrier family 25 member 38.
“Hereditary sideroblastic anemias are usually due to heme deficiency: X-linked sideroblastic anemia is caused by mutations in ALAS2, the first, rate-limiting enzyme of heme biosynthesis, while recessive forms are associated with mutations of mitochondria glycine importer solute carrier family 25 member 38.88”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [88]
Cites
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
The mitochondrial transporter family (SLC25): physiological and pathological implications
Palmieri, F. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1099-7 · Cited by 757 · see citing works
Reinders, J., Zahedi, R. P., Pfanner, N., Meisinger, C., & Sickmann, A. (2006) · Journal of Proteome Research · doi:10.1021/pr050477f · Cited by 394 · see citing works
Diseases caused by defects of mitochondrial carriers: A review
Palmieri, F. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.03.008 · Cited by 221 · see citing works
Haitina, T., Lindblom, J., Renström, T., & Fredriksson, R. (2006) · Genomics · doi:10.1016/j.ygeno.2006.06.016 · Cited by 182 · see citing works
The conserved substrate binding site of mitochondrial carriers
Kunji, E. R. S., & Robinson, A. J. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.021 · Cited by 172 · see citing works
Palmieri, F., Agrimi, G., Blanco, E., Castegna, A., Noia, M. A. D., Iacobazzi, V., Lasorsa, F. M., Marobbio, C. M. T., Palmieri, L., Scarcia, P., et al. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.05.023 · Cited by 169 · see citing works
The genetics of inherited sideroblastic anemias
Fleming, M. D. (2002) · Seminars in Hematology · doi:10.1053/shem.2002.35637 · Cited by 86 · see citing works
Self-citationMolecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia
Bottomley, S. S., May, B. K., Cox, T. C., Cotter, P. D., & Bishop, D. F. (1995) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf02110031 · Cited by 78 · see citing works
Self-citationRecent advances in the understanding of inherited sideroblastic anaemia
Camaschella, C. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07290.x · Cited by 77 · see citing works
Assessing Systems Properties of Yeast Mitochondria through an Interaction Map of the Organelle
Perocchi, F., Jensen, L. J., Gagneur, J., Ahting, U., von Mering, C., Peer Bork, B., Prokisch, H., & Steinmetz, L. M. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020170 · Cited by 76 · see citing works
MitoP2: An Integrative Tool for the Analysis of the Mitochondrial Proteome
Elstner, M., Andréoli, C., Ahting, U., Tetko, I. V., Klopstock, T., Meitinger, T., & Prokisch, H. (2008) · Molecular Biotechnology · doi:10.1007/s12033-008-9100-5 · Cited by 70 · see citing works
Congenital sideroblastic anemias.
Bottomley, S. S. (2006) · PubMed · Cited by 55 · see citing works
Self-citationLesuisse, E., Casteras-Simon, M., & Labbe, P. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1239 · Cited by 25 · see citing works
(2006) · Current Hepatology Reports · doi:10.1007/s11901-006-0001-4 · Cited by 11 · see citing works
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Two to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120 · see citing works
Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
The mitochondrial transporter family SLC25: Identification, properties and physiopathology
Palmieri, F. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.05.005 · Cited by 618 · see citing works
Richardson, D. R., Lane, D. J. R., Becker, E. M., Huang, M. L.-H., Whitnall, M., Rahmanto, Y. S., Sheftel, A. D., & Ponka, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912925107 · Cited by 536 · see citing works
“Actually, it has recently been shown that mutations in the putative glycine transporter, SLC25A38, lead to a rare form of sideroblastic anemia (106).”
BackgroundHeme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes
Chiabrando, D., Vinchi, F., Fiorito, V., Mercurio, S., & Tolosano, E. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00061 · Cited by 455 · see citing works
“Mutations in the gene coding for SLC25A38, the putative mitochondrial exporter of ALA, have been identified in patients with an autosomal recessive form of sideroblastic anemia (Guernsey et al., 2009).”
BackgroundMitochondria and Iron: current questions
Paul, B. T., Manz, D. H., Torti, F. M., & Torti, S. V. (2016) · Expert Review of Hematology · doi:10.1080/17474086.2016.1268047 · Cited by 429 · see citing works
Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease
Rouault, T. A. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009019 · Cited by 332 · see citing works
Molecular Mechanisms of Iron and Heme Metabolism
Dutt, S., Hamza, I., & Bartnikas, T. B. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062320-112625 · Cited by 337 · see citing works
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Ulirsch, J. C., Verboon, J. M., Kazerounian, S., Guo, M. H., Yuan, D., Ludwig, L. S., Handsaker, R. E., Abdulhay, N. J., Fiorini, C., Genovese, G., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.10.027 · Cited by 272 · see citing works
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Sachar, M., Anderson, K. E., & Ma, X. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.228130 · Cited by 259 · see citing works
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BackgroundOne ring to rule them all: Trafficking of heme and heme synthesis intermediates in the metazoans
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Ye, H., Jeong, S. Y., Ghosh, M. C., Kovtunovych, G., Silvestri, L., Ortillo, D., Uchida, N., Tisdale, J. F., Camaschella, C., & Rouault, T. A. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40372 · Cited by 239 · see citing works
Human Iron−Sulfur Cluster Assembly, Cellular Iron Homeostasis, and Disease
Ye, H., & Rouault, T. A. (2010) · Biochemistry · doi:10.1021/bi1004798 · Cited by 238 · see citing works
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Discoveries, metabolic roles and diseases of mitochondrial carriers: A review
Palmieri, F., & Monné, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.03.007 · Cited by 231 · see citing works
Maio, N., & Rouault, T. A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.09.009 · Cited by 215 · see citing works
SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts
Visconte, V., Makishima, H., Jankowska, A. M., Szpurka, H., Traina, F., Jerez, A., O'Keefe, C., Rogers, H. J., Sekeres, M. A., Maciejewski, J. P., et al. (2011) · Leukemia · doi:10.1038/leu.2011.232 · Cited by 212 · see citing works
Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis
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., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.012 · Cited by 213 · see citing works
“Defects in ALAS2, ABCB7, GLRX5, and SLC25A38 are each associated with different forms of sideroblastic anemias (Allikmets et al., 1999; Camaschella et al., 2007; Cotter et al., 1992; Guernsey et al., 2009), which are characterized by mitochondrial iron overload and impaired heme synthesis.”
Trafficking of Heme and Porphyrins in Metazoa
Severance, S., & Hamza, I. (2009) · Chemical Reviews · doi:10.1021/cr9001116 · Cited by 209 · see citing works
Mutations in Centrosomal Protein CEP152 in Primary Microcephaly Families Linked to MCPH4
Guernsey, D. L., Jiang, H., Hussin, J., Arnold, M., Bouyakdan, K., Perry, S., Babineau-Sturk, T., Beis, J., Dumas, N., Evans, S. C., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.06.003 · Cited by 200 · see citing works
“In other studies, we used dense SNP genotyping together with homozygosity analysis to map and identify causal mutations in patients with congenital sideroblastic anemia and cutis laxa type II in families from this region of eastern Canada.(44,45) The occurrence of a compound heterozygote among our three patients was u…”
MethodInfluentialSelf-citationPatnaik, M. M., Lasho, T. L., Hodnefield, J. M., Knudson, R. A., Ketterling, R. P., Garcia‐Manero, G., Steensma, D. P., Pardanani, A. D., Hanson, C. A., & Tefferi, A. (2011) · Blood · doi:10.1182/blood-2011-09-377994 · Cited by 201 · see citing works
“0001 RARS 48 (49) 35 (66) 13 (24) RCMD 43 (40) 16 (30) 27 (50) MDS-U 0 (0) 0 (0) 0 (0) RAEB-1 11 (10) 2 (4) 9 (17) RAEB-2 5 (5) 0 (0) 5 (9) Mutational analysis, n (%)”
Mitochondrial transporters of the SLC25 family and associated diseases: a review
Palmieri, F. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9708-5 · Cited by 197 · see citing works
“To date, 11 SLC25A38mutations have been detected in patients in which X-linked ALA synthase-2 gene alterations were absent (Guernsey et al 2009).”
BackgroundMitochondrial Iron in Human Health and Disease
Ward, D. M., & Cloonan, S. M. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114742 · Cited by 200 · see citing works
Control of intracellular heme levels: Heme transporters and heme oxygenases
Khan, A., & Quigley, J. G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.008 · Cited by 191 · see citing works
Mitochondrial metabolite transport
Palmieri, F., & Pierri, C. L. (2010) · Essays in Biochemistry · doi:10.1042/bse0470037 · Cited by 191 · see citing works
“In recent years, the rapid advance in the identifi cation of MC function has led to the disclosure of several diseases associated with defective carriers ([25] for a review; [26,27]).”
BackgroundIron and Copper in Mitochondrial Diseases
Xu, W., Barrientos, T., & Andrews, N. C. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.004 · Cited by 182 · see citing works
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Civelek, M., Wu, Y., Pan, C., Raulerson, C. K., Ko, A., He, A., Tilford, C. A., Saleem, N. K., Stančáková, A., Scott, L. J., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.01.027 · Cited by 173 · see citing works
“Missense mutations in SLC25A38, which encodes a mitochondrial solute carrier, lead to congenital sideroblastic anemia characterized by defective erythropoiesis and mitochondrial iron overload.(78) The function of SLC25A38 in adipose tissue remains unclear.”
BackgroundHeme and erythropoieis: more than a structural role
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Ineffective erythropoiesis and regulation of iron status in iron loading anaemias
Camaschella, C., & Nai, A. (2016) · British Journal of Haematology · doi:10.1111/bjh.13820 · Cited by 172 · see citing works
“Ineffective erythropoiesis characterizes patients with inherited sideroblastic anaemia who do not correctly utilize mitochondrial iron because of mutations of players in the first steps of haem synthesis, delta-aminolevulinate synthase 2 (ALAS2) or the glycine importer SLC25A38 (Guernsey et al, 2009).”
BackgroundBiologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms
Cazzola, M., Rossi, M., & Malcovati, L. (2012) · Blood · doi:10.1182/blood-2012-09-399725 · Cited by 151 · see citing works
Iron regulatory proteins secure mitochondrial iron sufficiency and function
Galy, B., Ferring-Appel, D., Sauer, S. W., Kaden, S., Lyoumi, S., Puy, H., Kölker, S., Gröne, H.-J., & Hentze, M. W. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.06.007 · Cited by 147 · see citing works
“, the Grx5, Slc25A38, or Abcb7 genes (Guernsey et al., 2009; Levi andRovida, 2009;Rouault andTong, 2008;Sheftel and Lill, 2009).”
From Synthesis to Utilization: The Ins and Outs of Mitochondrial Heme
Swenson, S. A., Moore, C. M., Marcero, J. R., Medlock, A. E., Reddi, A. R., & Khalimonchuk, O. (2020) · Cells · doi:10.3390/cells9030579 · Cited by 148 · see citing works
“Glycine is transported into the intermembrane space of the mitochondria (IMS) through an unknown mechanism and is transported across the inner mitocho drial membrane (IMM) by SLC25A38.”
BackgroundRestored iron transport by a small molecule promotes absorption and hemoglobinization in animals
Grillo, A. S., SantaMaria, A. M., Kafina, M. D., Cioffi, A. G., Huston, N. C., Han, M., Seo, Y. A., Yien, Y. Y., Nardone, C., Menon, A. V., et al. (2017) · Science · doi:10.1126/science.aah3862 · Cited by 147 · see citing works
Bergmann, A. K., Campagna, D. R., McLoughlin, E. M., Agarwal, S., Fleming, M. D., Bottomley, S. S., & Neufeld, E. J. (2009) · Pediatric Blood & Cancer · doi:10.1002/pbc.22244 · Cited by 139 · see citing works
“As reported separately [7], the discovery that molecular defects in the mitochondrial carrier family gene SLC25A38 are associated with non-syndromic, autosomal recessive CSA led to the identification of multiple biallelic mutations in this gene in three distinct families and nine additional unrelated individuals from…”
BackgroundInfluentialSelf-citationRegulation of Amino Acid Transport in Saccharomyces cerevisiae
Bianchi, F., Klooster, J. S. V. ’., Ruiz, S. J., & Poolman, B. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00024-19 · Cited by 142 · see citing works
“Cells lacking hem25 exhibit a defect in respiration and decreased stability of specific proteins of the electron transport chain (114, 115).”
BackgroundPhysiological and pathological roles of mitochondrial SLC25 carriers
Gutiérrez‐Aguilar, M., & Baines, C. P. (2013) · Biochemical Journal · doi:10.1042/bj20121753 · Cited by 140 · see citing works
Iron and Porphyrin Trafficking in Heme Biogenesis
Schultz, I. J., Chen, C., Paw, B. H., & Hamza, I. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.119503 · Cited by 129 · see citing works
Iron metabolism and related genetic diseases: A cleared land, keeping mysteries
Brissot, P., & Loréal, O. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.009 · Cited by 126 · see citing works
“OTHER DISEASES They correspond to disturbances in heme synthesis, encompassing some forms of : i) congenital sideroblastic anemias ( by mutations of the following genes ALAS2(107), SLC25A38(108), ABCB7 (109), glutaredoxine 5 (110)), and ii) hereditary porphyrias(111).”
BackgroundErythroid Heme Biosynthesis and Its DisordersPreprint
Dailey, H. A., & Meissner, P. N. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011676 · Cited by 127 · see citing works
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BackgroundWiseman, D. H., May, A. M., Jolles, S. R. A., Connor, P., Powell, C., Heeney, M. M., Giardina, P. J., Klaassen, R. J., Chakraborty, P. K., Geraghty, M. T., et al. (2013) · Blood · doi:10.1182/blood-2012-08-439083 · Cited by 122 · see citing works
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BackgroundSelf-citationPalmieri, F., & Pierri, C. L. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.10.063 · Cited by 124 · see citing works
“cerevisiae demonstrating that SLC25A38p plays a role in heme biosynthesis [52].”
BackgroundInfluentialErythroid cell mitochondria receive endosomal iron by a “kiss-and-run” mechanism
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Bottomley, S. S., & Fleming, M. D. (2014) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2014.04.008 · Cited by 120 · see citing works
Self-citationMitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis
Kardon, J. R., Yien, Y. Y., Huston, N. C., Branco, D. S., Hildick-Smith, G. J., Rhee, K. Y., Paw, B. H., & Baker, T. A. (2015) · Cell · doi:10.1016/j.cell.2015.04.017 · Cited by 116 · see citing works
“…HEM1 ( the gene encoding ALAS (EC 2.3.1.37) ( Arrese et al., 1983)); HEM25 (encoding the putative mitochondrial glycine/ALA transporter SLC25A38 (Guernsey et al., 2009)); and HEM2 (encoding the cytosolic enzyme that catalyzes the second step in heme biosynthesis, ALA dehydrdatase (ALAD; EC…”
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Ducamp, S., & Fleming, M. D. (2019) · Blood · doi:10.1182/blood-2018-08-815951 · Cited by 136 · see citing works
Self-citationRole of Heme in Cardiovascular Physiology and Disease
Sawicki, K. T., Chang, H., & Ardehali, H. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001138 · Cited by 111 · see citing works
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BackgroundCongenital Sideroblastic Anemias: Iron and Heme Lost in Mitochondrial Translation
Fleming, M. D. (2011) · Hematology · doi:10.1182/asheducation-2011.1.525 · Cited by 103 · see citing works
Self-citationMitochondrial Mayhem: The Mitochondrion as a Modulator of Iron Metabolism and Its Role in Disease
Huang, M. L.-H., Lane, D. J. R., & Richardson, D. R. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.3921 · Cited by 103 · see citing works
“It is worth noting that a new form of human sideroblastic anemia has been recently identified to be due to the mutation in an erythroid specific mitochondrial transport protein, SLC25A38 (55).”
Zhao, Y., Tseng, I.-C., Heyser, C. J., Rockenstein, E., Mante, M., Adame, A., Zheng, Q., Huang, T., Wang, X., Arslan, P. E., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.020 · Cited by 98 · see citing works
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BackgroundMitochondrial iron metabolism and its role in diseases
Gao, J., Zhou, Q., Wu, D., & Chen, L. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.12.005 · Cited by 103 · see citing works
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Camaschella, C., Pagani, A., Nai, A., & Silvestri, L. (2016) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12505 · Cited by 97 · see citing works
“The X-linked form is due to delta-aminolevulinic acid synthase 2 deficiency, while the recessive form is due to mutations of the mitochondrial glycine importer SLC25A38 [18].”
Heme metabolism and erythropoiesis
Chung, J., Chen, C., & Paw, B. H. (2012) · Current Opinion in Hematology · doi:10.1097/moh.0b013e328351c48b · Cited by 92 · see citing works
Lunetti, P., Damiano, F., Benedetto, G. E. D., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.736876 · Cited by 93 · see citing works
“Furthermore, an anemic phenotype similar to that of ALAS2 deficiency has also been observed in the knockdown of two zebrafish orthologues of SLC25A38 (slc25a38a and slc25a38b), indicating that this gene is important for red blood cell production and function (13, 14).”
BackgroundInfluentialHereditary Sideroblastic Anemias: Pathophysiology, Diagnosis, and Treatment
Camaschella, C. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.07.001 · Cited by 91 · see citing works
Iron disorders of genetic origin: a changing world
Brissot, P., Bardou‐Jacquet, E., Jouanolle, A., & Loréal, O. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.07.004 · Cited by 84 · see citing works
Donker, A. E., Raymakers, R. A. P., Vlasveld, L. T., van Barneveld, T., Terink, R., Dors, N., Brons, P., Knoers, N. V. A. M., & Swinkels, D. W. (2014) · Blood · doi:10.1182/blood-2014-01-548776 · Cited by 86 · see citing works
Kaneko, K., Furuyama, K., Fujiwara, T., Kobayashi, R., Ishida, H., Harigae, H., & Shibahara, S. (2013) · Haematologica · doi:10.3324/haematol.2013.085449 · Cited by 82 · see citing works
Patnaik, M. M., & Tefferi, A. (2017) · American Journal of Hematology · doi:10.1002/ajh.24637 · Cited by 81 · see citing works
“Loss of function mutations in SLC25A38 have been shown to cause a sideroblastic anemia (SA) similar to XLSA, but with an autosomal recessive inheritance.(10) XLSA with ataxia is an inherited disorder associated with SA and non-progressive spinocerebellar ataxia (cerebellar hypoplasia), secondary to mutations involving…”
BackgroundPatnaik, M. M., Hanson, C. A., Sulai, N. H., Hodnefield, J. M., Knudson, R. A., Ketterling, R. P., Lasho, T. L., & Tefferi, A. (2012) · Blood · doi:10.1182/blood-2012-03-415356 · Cited by 79 · see citing works
Mitochondrial iron overload: causes and consequences
Rouault, T. A. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.02.004 · Cited by 78 · see citing works
Hereditary sideroblastic anemia: pathophysiology and gene mutations
Harigae, H., & Furuyama, K. (2010) · International Journal of Hematology · doi:10.1007/s12185-010-0688-4 · Cited by 75 · see citing works
“Recently, Guernsey [11] carried out SNP-based genomewide scans in subjects with familial or sporadic congenital sideroblastic anemia, and identified several mutations of the SLC25A38 gene.”
BackgroundThe circadian protein CLOCK regulates cell metabolism via the mitochondrial carrier SLC25A10
Cai, T., Hua, B., Luo, D., Xu, L., Cheng, Q., Yuan, G., Yan, Z., Sun, N., Hua, L., & Lü, C. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.03.016 · Cited by 74 · see citing works
Ducamp, S., Kannengiesser, C., Touati, M., Garçon, L., Guerci‐Bresler, A., Guichard, J. F., Vermylen, C., Dochir, J., Poirel, H. A., Fouyssac, F., et al. (2011) · Human Mutation · doi:10.1002/humu.21455 · Cited by 69 · see citing works
“…32, No. 6, 590–597, 2011 593 (MIM] 205950): a homozygous mutation was found in GLRX5 in a consanguineous proband [Camaschella et al., 2007], and SLC25A38, which encodes a putative glycine transporter, was found to be mutated in the affected members of different families [Guernsey et al., 2009].”
BackgroundRing sideroblasts and sideroblastic anemias
Cazzola, M., & Invernizzi, R. (2011) · Haematologica · doi:10.3324/haematol.2011.044628 · Cited by 71 · see citing works
Appoptosin is a Novel Pro-Apoptotic Protein and Mediates Cell Death in Neurodegeneration
Zhang, H., Zhang, Y.-W., Chen, Y., Huang, X., Zhou, F., Wang, W., Xian, B., Zhang, X., Masliah, E., Chen, Q., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3668-12.2012 · Cited by 68 · see citing works
“Appoptosin is highly abundantly expressed in blood cells (Guernsey et al., 2009).”
BackgroundInfluentialGlycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia
Fernández-Murray, J. P., Prykhozhij, S. V., Dufay, J. N., Steele, S. L., Gaston, D., Nasrallah, G. K., Coombs, A. J., Liwski, R., Fernandez, C. V., Berman, J. N., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005783 · Cited by 68 · see citing works
“Morpholino knockdown of both slc25a38a and slc25a38b was required to produce an anemia in zebrafish embryos as determined using o-dianisidine staining to assess hemoglobin content (Fig 6B and [6]).”
Self-citationMitochondrial Carriers for Aspartate, Glutamate and Other Amino Acids: A Review
Monné, M., Vozza, A., Lasorsa, F. M., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184456 · Cited by 66 · see citing works
“This finding led to speculate that the MC SLC25A38 could be involved in heme and iron-sulfur cluster biogenesis, possibly by transporting glycine [106].”
BackgroundZebrafish as a model system for mitochondrial biology and diseases
Steele, S. L., Prykhozhij, S. V., & Berman, J. N. (2013) · Translational research · doi:10.1016/j.trsl.2013.08.008 · Cited by 65 · see citing works
Regulation of Heme Synthesis by Mitochondrial Homeostasis Proteins
Yien, Y. Y., & Perfetto, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.895521 · Cited by 63 · see citing works
Intracellular iron and heme trafficking and metabolism in developing erythroblasts
Kafina, M. D., & Paw, B. H. (2017) · Metallomics · doi:10.1039/c7mt00103g · Cited by 62 · see citing works
The SoLute Carrier (SLC) Family Series in Teleost Fish
Verri, T., Terova, G., Romano, A., Barca, A., Pisani, P., Storelli, C., & Saroglia, M. G. (2012) · Wiley eBooks · doi:10.1002/9781118350041.ch10 · Cited by 60 · see citing works
Abu-Zeinah, G. F., & DeSancho, M. T. (2020) · Journal of Blood Medicine · doi:10.2147/jbm.s232644 · Cited by 60 · see citing works
Kannengiesser, C., Sánchez, M., Sweeney, M. C., et al. (2011) · Haematologica · doi:10.3324/haematol.2010.039164 · Cited by 60 · see citing works
Inherited disorders of iron metabolism
Camaschella, C., & Poggiali, E. (2011) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283425591 · Cited by 59 · see citing works
The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism
Acoba, M. G., Alpergin, E. S. S., Renuse, S., Fernández-del-Río, L., Lu, Y., Khalimonchuk, O., Clarke, C. F., Pandey, A., Wolfgang, M. J., & Claypool, S. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108869 · Cited by 59 · see citing works
Patnaik, M. M., & Tefferi, A. (2021) · American Journal of Hematology · doi:10.1002/ajh.26090 · Cited by 56 · see citing works
Pathophysiology and genetic mutations in congenital sideroblastic anemia
Fujiwara, T., & Harigae, H. (2013) · Pediatrics International · doi:10.1111/ped.12217 · Cited by 53 · see citing works
Rare anemias due to genetic iron metabolism defects
Brissot, P., Bernard, D. G., Brissot, É., Loréal, O., & Troadec, M. (2018) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2018.06.003 · Cited by 51 · see citing works
Biology of Heme in Mammalian Erythroid Cells and Related Disorders
Fujiwara, T., & Harigae, H. (2015) · BioMed Research International · doi:10.1155/2015/278536 · Cited by 53 · see citing works
“Yeast lacking the SLC25A38 ortholog YDL119c exhibits a defect in ALA biogenesis [21], suggesting that SLC25A38 is required for glycine import.”
BackgroundRegulation of mitochondrial iron homeostasis by sideroflexin 2
Mon, E. E., Wei, F., Ahmad, R. N. R., Yamamoto, T., Moroishi, T., & Tomizawa, K. (2018) · The Journal of Physiological Sciences · doi:10.1007/s12576-018-0652-2 · Cited by 52 · see citing works
X‐linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA‐binding site mutations
Campagna, D. R., de Bie, C. I., Schmitz‐Abe, K., Sweeney, M. C., Sendamarai, A. K., Schmidt, P. J., Heeney, M. M., Yntema, H. G., Kannengiesser, C., Grandchamp, B., et al. (2013) · American Journal of Hematology · doi:10.1002/ajh.23616 · Cited by 50 · see citing works
“Male probands did not have mutations in the exons and intron–exon boundaries of ALAS2 or GLRX5 (all families) or SLC25A38 (families A, F, P, and N) [11,12].”
BackgroundSelf-citationA Recap of Heme Metabolism towards Understanding Protoporphyrin IX Selectivity in Cancer Cells
Kiening, M., & Lange, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147974 · Cited by 48 · see citing works
“Previous studies suggested that SLC25A38 facilitates the exchange of glycine and 5-ALA through the mitochondrial membrane [21] and that the ATP-binding cassette subfamily B member 10 (ABCB10) is essential for 5-ALA export to the cytoplasm [22].”
BackgroundMolecular pathophysiology and genetic mutations in congenital sideroblastic anemia
Fujiwara, T., & Harigae, H. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.008 · Cited by 47 · see citing works
Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism
Hewton, K. G., Johal, A. S., & Parker, S. J. (2021) · Metabolites · doi:10.3390/metabo11020112 · Cited by 49 · see citing works
“Mutations in SLC25A38 give rise to congenital sideroblastic anemia, caused by a defect in heme biosynthesis [212].”
BackgroundShamseldin, H. E., Smith, L. L., Kentab, A. Y., Alkhalidi, H., Summers, B. J., Alsedairy, H., Xiong, Y., Gupta, V., & Alkuraya, F. S. (2015) · Human Genetics · doi:10.1007/s00439-015-1608-8 · Cited by 47 · see citing works
“…(HHH) syndrome, Amish microcephaly , carnitine/acylcarnitine carrier deficiency, early epileptic encephalopathy and sideroblastic anemia, respectively (Camacho et al. 1999; Guernsey et al. 2009; Huizing et al. 1997; Kobayashi et al. 1999; Molinari et al. 2005; Rosenberg et al. 2002).”
Synthesis, delivery and regulation of eukaryotic heme and Fe–S cluster cofactors
Barupala, D., Dzul, S. P., Riggs-Gelasco, P. J., & Stemmler, T. L. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.01.010 · Cited by 46 · see citing works
Refractory anemia with ring sideroblasts and RARS with thrombocytosis
Patnaik, M. M., & Tefferi, A. (2015) · American Journal of Hematology · doi:10.1002/ajh.24038 · Cited by 45 · see citing works
20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport
Cunningham, C. N., & Rutter, J. P. (2020) · EMBO Reports · doi:10.15252/embr.202050071 · Cited by 44 · see citing works
“Consistent with this expression pattern, zebrafish SLC25A38 knockouts are anemic and phenocopy non-syndromic congenital sideroblastic anemia [88].”
Patnaik, M. M., & Tefferi, A. (2019) · American Journal of Hematology · doi:10.1002/ajh.25397 · Cited by 45 · see citing works
“SLC25A38 have been shown to cause a sideroblastic anemia (SA) similar to XLSA, but with an autosomal recessive inheritance.(10)”
BackgroundHow I manage patients with atypical microcytic anaemia
Camaschella, C. (2013) · British Journal of Haematology · doi:10.1111/bjh.12081 · Cited by 49 · see citing works
Cazzola, M., & Malcovati, L. (2015) · Hematology · doi:10.1182/asheducation-2015.1.19 · Cited by 44 · see citing works
Peoc’h, K., Nicolas, G., Schmitt, C., Mirmiran, A., Daher, R., Lefèbvre, T., Gouya, L., Karim, Z., & Puy, H. (2019) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2019.01.015 · Cited by 42 · see citing works
Mitochondrial Iron Metabolism and Sideroblastic Anemia
Sheftel, A. D., Richardson, D. R., Prchal, J. T., & Ponka, P. (2009) · Acta Haematologica · doi:10.1159/000243796 · Cited by 41 · see citing works
“all can result in mitochondrial iron accumulation in developing red blood cells. In a recent paper, Guernsey et al. [”
BackgroundFiermonte, G., Parisi, G., Martinelli, D., et al. (2011) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2011.08.022 · Cited by 42 · see citing works
“G72E in the SLC25A3_PiC deficiency [31], G130E in the SLC25A38 associated to congenital sideroblastic anemia [32], G236W in the SLC25A22_GC1 associated to the neonatal myoclonic epilepsy [33], G125S in the SLC25A19_TPC associated to the neuropathy and bilateral striatal necrosis [34], G113C, G216S, G220R in the SLC25A…”
BackgroundThe Porphyrias and Other Disorders of Porphyrin Metabolism
Badminton, M. N., Whatley, S. D., Deacon, A. C., et al. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4160-6164-9.00033-0 · Cited by 41 · see citing works
Ren, Y., Yang, S., Tan, G., Ye, W., Liu, D., Xu, Q., Ding, Z., Zhong, Y., Zhang, J., Jiang, D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029666 · Cited by 41 · see citing works
“, Fiedreich’s ataxia (FRDA), Sideroblastic anemias (SA), ISCU Myopathy, Alzheimer’s Disease (AD), Parkinson’s disease (PD) and Multiple Sclerosis (MS) [6–12].”
BackgroundOhba, R., Furuyama, K., Yoshida, K., Fujiwara, T., Fukuhara, N., Onishi, Y., Manabe, A., Ito, E., Ozawa, K., Kojima, S., et al. (2012) · Annals of Hematology · doi:10.1007/s00277-012-1564-5 · Cited by 40 · see citing works
“To date, mutations of genes involved in heme biosynthesis, Fe–S cluster biogenesis, or the biology of mitochondria have been reported in CSA [1–5].”
BackgroundRefractory anemia with ring sideroblasts
Malcovati, L., & Cazzola, M. (2013) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2013.09.005 · Cited by 40 · see citing works
“Other genes responsible for inherited sideroblastic anemia include ABCB7, mutated in the X-linked sideroblastic anemia associated with spinocerebellar ataxia [10], and SLC25A38, mutated in autosomal recessive, pyridoxine refractory, congenital sideroblastic anemia [11].”
Background
- Authors
- Guernsey, D. L., Jiang, H., Campagna, D. R., Evans, S. C., Ferguson, M., Kellogg, M. D., Lachance, M., Matsuoka, M., Nightingale, M., Rideout, A., Saint-Amant, L., Schmidt, P. J., Orr, A., Bottomley, S. S., Fleming, M. D., Ludman, M., Dyack, S., Fernandez, C. V., & Samuels, M. E.
- Affiliations
- Dalhousie University (CA)
- Boston Children's Hospital (US)
- Izaak Walton Killam Health Centre (CA)
- Université de Montréal (CA)
- University of Oklahoma (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Corresponding author
- Samuels, Mark E
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-05-03
- Volume
- 41
- Issue
- 6
- Pages
- 651-653
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1977142594
- Semantic Scholar
- 3ae7bb0c799e0bd800d34f99c145dd5d90c73263
- Cited by
- 244
- References
- 15
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 14 · 2021: 15 · 2020: 14 · 2019: 14 · 2018: 14 · 2017: 15 · 2016: 19 · 2015: 18 · 2014: 11 · 2013: 19 · 2012: 16
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080011, K01DK074410)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- SLC25A38, mitochondrial carrier family, congenital sideroblastic anemia, autosomal recessive inheritance, ring sideroblasts, heme biosynthesis, positional cloning, genetic mutations
- MeSH terms
- Anemia, Sideroblastic, Animals, Carrier State, Family, Fishes, Heme, Humans, Mutation, Phenotype, Yeasts, Mitochondrial Membrane Transport Proteins
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