The mutual control of iron and erythropoiesis

International Journal of Laboratory Hematology

Volumn 38, Issue , 2016, Pages 20-26

  Camaschella, C ^a   Pagani, A ^a   Nai, A ^a   Silvestri, L ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Anemia; erythropoiesis; erythropoietin; iron; transferrin

Indexed keywords

BONE MORPHOGENETIC PROTEIN; ERYTHROPOIETIN; HEME; HEMOGLOBIN ALPHA CHAIN; HEPCIDIN; IRON; RNA; SMAD PROTEIN; TRANSFERRIN; TRANSFERRIN RECEPTOR; TRANSFERRIN RECEPTOR 2;

ANEMIA; ERYTHROBLAST; ERYTHROID CELL; ERYTHROPOIESIS; GLOBIN SYNTHESIS; HEMOGLOBIN SYNTHESIS; HOMEOSTASIS; HUMAN; HYPOXIA; HYPOXIC CELL; IRON DEFICIENCY; IRON HOMEOSTASIS; IRON OVERLOAD; IRON RESTRICTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SENSITIVITY ANALYSIS; THALASSEMIA;

EID: 84978388601     PISSN: 17515521     EISSN: 1751553X     Source Type: Journal    
DOI: 10.1111/ijlh.12505     Document Type: Review

References (45)

1. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell 2010;142:24–38.
2. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;373:485–6.
3. Jenkitkasemwong S, Wang CY, Coffey R, Zhang W, Chan A, Biel T, Kim JS, Hojyo S, Fukada T, Knutson MD. SLC39A14 is required for the development of hepatocellular iron overload in murine models of hereditary hemochromatosis. Cell Metab 2015;22:138–50.
4. 2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nat Med 2003;9:1187–94.
5. Camaschella C, Nai A. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. Br J Haematol 2015;172:512–23.
6. Bartnikas TB, Andrews NC, Fleming MD. Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice. Blood 2011;117:630–7.
7. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet 1999;21:396–9.
8. Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Rep 2015;13:533–45.
9. Barrientos T, Laothamatas I, Koves TR, Soderblom EJ, Bryan M, Moseley MA, Muoio DM, Andrews NC. Metabolic catastrophe in mice lacking transferrin receptor in muscle. EBioMedicine 2015;2:1705–17.
10. Chen AC, Donovan A, Ned-Sykes R, Andrews NC. Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis. Proc Natl Acad Sci USA 2015;112:11714–9.
11. Iolascon A, d'Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C. Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood 2006;107:349–54.
12. Grandchamp B, Hetet G, Kannengiesser C, Oudin C, Beaumont C, Rodrigues-Ferreira S, Amson R, Telerman A, Nielsen P, Kohne E, Balser C, Heimpel H. A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene. Blood 2011;118:6660–6.
13. Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ, Wang X, Liu Y, Goessling W, Kimmelman AC, Harper JW. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife 2015. doi: 10.7554/eLife.10308.
14. Anderson SA, Nizzi CP, Chang YI, Deck KM, Schmidt PJ, Galy B, Damnernsawad A, Broman AT, Kendziorski C, Hentze MW, Fleming MD, Zhang J, Eisenstein RS. The IRP1-HIF-2alpha axis coordinates iron and oxygen sensing with erythropoiesis and iron absorption. Cell Metab 2013;17:282–90.
15. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, Mayo MM, Samuel SM, Strouse JJ, Markianos K, Andrews NC, Fleming MD. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008;40:569–71.
16. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab 2008;8:502–11.
17. De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C. Iron refractory iron deficiency anemia. Haematologica 2013;98:845–53.
18. Guernsey DL, Jiang H, Campagna DR, Evans SC, Ferguson M, Kellogg MD, Lachance M, Matsuoka M, Nightingale M, Rideout A, Saint-Amant L, Schmidt PJ, Orr A, Bottomley SS, Fleming MD, Ludman M, Dyack S, Fernandez CV, Samuels ME. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet 2009;41:651–3.
19. Maio N, Rouault TA. Iron-sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery. Biochim Biophys Acta 2015;1853:1493–512.
20. Ye H, Jeong SY, Ghosh MC, Kovtunovych G, Silvestri L, Ortillo D, Uchida N, Tisdale J, Camaschella C, Rouault TA. Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest 2010;120:1749–61.
21. Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol 2008;143:27–38.
22. Camaschella C. How I manage patients with atypical microcytic anaemia. Br J Haematol 2013;160:12–24.
23. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730–5.
24. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 2007;92:583–8.
25. Keel SB, Doty R, Liu L, Nemeth E, Cherian S, Ganz T, Abkowitz JL. Evidence that the expression of transferrin receptor 1 on erythroid marrow cells mediates hepcidin suppression in the liver. Exp Hematol 2015;43:469–78.
26. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, Moroney JW, Reed CH, Luban NL, Wang RH, Eling TE, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007;13:1096–101.
27. Casanovas G, Vujic Spasic M, Casu C, Rivella S, Strelau J, Unsicker K, Muckenthaler MU. The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice. Haematologica 2013;98:444–7.
28. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014;46:678–84.
29. Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012;287:11968–80.
30. Kautz L, Jung G, Nemeth E, Ganz T. Erythroferrone contributes to recovery from anemia of inflammation. Blood 2014;124:2569–74.
31. Kautz L, Jung G, Du X, Gabayan V, Chapman J, Nasoff M, Nemeth E, Ganz T. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of beta-thalassemia. Blood 2015;126:2031–7.
32. Nai A, Rubio A, Campanella A, Gourbeyre O, Artuso I, Bordini J, Gineste A, Latour C, Besson-Fournier C, Lin HY, Coppin H, Roth MP, Camaschella C, Silvestri L, Meynard D. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice. Blood 2016. doi: 10.1182/blood-2015-11-681494.
33. Silvestri L, Pagani A, Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 2008;111:924–31.
34. Lin L, Nemeth E, Goodnough JB, Thapa DR, Gabayan V, Ganz T. Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. Blood Cells Mol Dis 2008;40:122–31.
35. Sonnweber T, Nachbaur D, Schroll A, Nairz M, Seifert M, Demetz E, Haschka D, Mitterstiller AM, Kleinsasser A, Burtscher M, Trubsbach S, Murphy AT, Wroblewski V, Witcher DR, Mleczko-Sanecka K, Vecchi C, Muckenthaler MU, Pietrangelo A, Theurl I, Weiss G. Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB. Gut 2014;63:1951–9.
36. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 2000;25:14–5.
37. Forejtnikova H, Vieillevoye M, Zermati Y, Lambert M, Pellegrino RM, Guihard S, Gaudry M, Camaschella C, Lacombe C, Roetto A, Mayeux P, Verdier F. Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis. Blood 2010;116:5357–67.
38. Nai A, Lidonnici MR, Rausa M, Mandelli G, Pagani A, Silvestri L, Ferrari G, Camaschella C. The second transferrin receptor regulates red blood cell production in mice. Blood 2015;125:1170–9.
39. Johnson MB, Enns CA. Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 2004;104:4287–93.
40. Pagani A, Vieillevoye M, Nai A, Rausa M, Ladli M, Lacombe C, Mayeux P, Verdier F, Camaschella C, Silvestri L. Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form. Haematologica 2015;100:458–65.
41. Chen J, Enns CA. CD81 promotes both the degradation of transferrin receptor 2 (TfR2) and the Tfr2-mediated maintenance of hepcidin expression. J Biol Chem 2015;290:7841–50.
42. Zhao N, Nizzi CP, Anderson SA, Wang J, Ueno A, Tsukamoto H, Eisenstein RS, Enns CA, Zhang AS. Low intracellular iron increases the stability of matriptase-2. J Biol Chem 2015;290:4432–46.
43. Schmidt PJ, Toudjarska I, Sendamarai AK, Racie T, Milstein S, Bettencourt BR, Hettinger J, Bumcrot D, Fleming MD. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine beta-thalassemia intermedia. Blood 2013;121:1200–8.
44. Guo S, Casu C, Gardenghi S, Booten S, Aghajan M, Peralta R, Watt A, Freier S, Monia BP, Rivella S. Reducing TMPRSS6 ameliorates hemochromatosis and beta-thalassemia in mice. J Clin Invest 2013;123:1531–41.
45. Ramos E, Ruchala P, Goodnough JB, Kautz L, Preza GC, Nemeth E. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood 2012;120:3829–36.