An iron-regulated ferric reductase associated with the absorption of dietary iron
Abstract
The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Iron homeostasis and bioavailability to either the host or invading pathogens is tightly regulated through coordination of hepcidin, iron binding proteins, and several enzymes involved in iron metabolism.
“Iron homeostasis and bioavailability to either the host or invading pathogens is tightly regulated through coordination of hepcidin, iron binding proteins and several enzymes involved in iron metabolism (McKie et al., 2001; Nemeth et al., 2004).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as McKie et al., 2001
Uptake of ionic non-heme iron is a sequential process: ferric iron is reduced by DCYTB at the luminal surface of enterocytes, and DMT1 imports iron into the cytoplasm.
“The uptake of ionic NHI in contrast, is a sequential process that is well characterized: Following the reduction of ferric iron by DCYTB (for duodenal cytochrome B) at the luminal surface of enterocytes (ENT), it is DMT1 (for divalent metal transporter-1) that imports iron into the cytoplasm (Gunshin et al., 1997;McKie et al., 2001).”
From Iron in infection and immunity (2020) · cites this paper as McKie et al., 2001
When systemic iron levels in the blood stream are low, expression of DMT1 and DcytB ferrireductase increases on the surface of intestinal enterocytes on the luminal side, enabling reduction of Fe3+ to Fe2+ which can then be taken up by DMT1.
“When systemic iron levels in the blood stream are low, expression of DMT1 (divalent metal transporter 1, also called NRAMP2 as well as SLC11A2) and DcytB (duodenal membrane associated cytochrome-b) ferrireductase increases on the surface of intestinal enterocytes on the luminal side enabling the reduction of Fe3+ into its ferrous form (Fe2+) which can then be taken up by DMT1 (McKie et al., 2001).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as McKie et al., 2001
Dmt1 only accepts ferrous iron along with other divalent cations and co-localizes with an iron reductase.
“At either location, Dmt1 only accepts ferrous iron along with other divalent cations, such as copper or manganese, and co-localizes with an iron reductase [152, 177].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [152]
DCYTB enzymes present within the apical membrane of enterocytes are able to reduce soluble Fe3+ to Fe2+ before DMT1-mediated Fe2+ import.
“To overcome the low availability of Fe2+, duodenal cytochrome b (DCYTB) enzymes that are present within the apical membrane of enterocytes are able to reduce any soluble Fe3+ to Fe2+ before DMT1‐mediated Fe2+ import. 14 , 15”
From The battle for iron in enteric infections (2020) · cites this paper as [14]
Inorganic iron uptake from the gastrointestinal lumen by enterocytes depends upon DMT1, which is not able to import Fe3+.
“However, inorganic iron uptake from the gastrointestinal lumen by enterocytes depends upon the divalent metal transporter protein 1 (DMT1 or NRAMP2), which is not able to import Fe3+. 12 , 13 , 14”
From The battle for iron in enteric infections (2020) · cites this paper as [14]
Mammals take up dietary ferrous iron through DMT1 expressed by duodenal enterocytes.
“Mammals acquire ferrous (Fe2+) from the diet via a mechanism assisted by the divalent metal transporter ion transporter 1 (DMT1) expressed by duodenum enterocytes (12, 13).”
From Innate Nutritional Immunity (2018) · cites this paper as [13]
Ferric iron must be reduced to ferrous iron, either chemically or through the action of a brush border ferrireductase such as CYBRD1/DCYTB, a cytochrome B561 homolog that may use ascorbic acid as a cofactor.
“It must be reduced to ferrous (Fe 2ϩ ) iron, either chemically or through the action of a brush border ferrireductase such as duodenal cytochrome B (CYBRD1, also known as DCYTB), a cytochrome B561 homolog that may use ascorbic acid as a cofactor.53”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [53]
CYBRD1 was one of 2 iron transport-related molecules discovered by McKie through a very productive RNA subtraction approach.
“CYBRD1 was one of 2 iron transport-related molecules discovered by McKie through a very productive RNA subtraction approach.53,54”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [53]
IRP1-knockout mice survived with insignificant effects on iron homeostasis in kidney and brown fat.
“IRP1-knockout mice survived with insignificant effects on iron homeostasis in kidney and brown fat that highly express IRP1 (55, 200).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [200]
IRP2-knockout mice showed abnormal induction of ferritin expression, resulting in iron misregulation in intestinal mucosa and the CNS.
“IRP2-knockout mice showed abnormal induction of ferritin expression, resulting in iron misregulation in intestinal mucosa and the CNS (55, 200).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [200]
IRP2 is the predominant posttranscriptional regulator of key genes involved in iron homeostasis.
“IRP2 was also sensitive to iron levels, whereas IRP1 was not, suggesting that IRP2 is the predominant posttranscriptional regulator of key genes involved iron homeostasis (200).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [200]
IRP2 is sensitive to iron levels, whereas IRP1 is not.
“IRP2 was also sensitive to iron levels, whereas IRP1 was not, suggesting that IRP2 is the predominant posttranscriptional regulator of key genes involved iron homeostasis (200).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [200]
IRP1-knockout mice misregulate iron in brown fat and kidney, whereas IRP2-knockout mice exhibit aberrant management of iron in multiple tissues.
“IRP1-knockout mice misregulate iron in specific tissues, namely in brown fat and kidney, whereas IRP2-knockout mice exhibit aberrant management of iron in multiple tissues.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [200]
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166 · see citing works
Self-citationMcKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422 · see citing works
Self-citationA ferric-chelate reductase for iron uptake from soils
Robinson, N. J., Procter, C. M., Connolly, E. L., & Guerinot, M. L. (1999) · Nature · doi:10.1038/17800 · Cited by 1,271 · see citing works
Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene
Fleming, M. D., Trenor, C. C., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., & Andrews, N. C. (1997) · Nature Genetics · doi:10.1038/ng0897-383 · Cited by 1,159 · see citing works
Dancis, A., Roman, D. G., Anderson, G. J., Hinnebusch, A. G., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.3869 · Cited by 358 · see citing works
Identification and characterization of a second mouse Nramp gene
Gruenheid, S., Cellier, M. F., Vidal, S. M., & Gros, P. (1995) · Genomics · doi:10.1016/0888-7543(95)80053-o · Cited by 287 · see citing works
Georgatsou, E., & Alexandraki, D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3065-3073.1994 · Cited by 233 · see citing works
Trinder, D., Oates, P. S., Thomas, C., Sadleir, J., & Morgan, E. H. (2000) · Gut · doi:10.1136/gut.46.2.270 · Cited by 230 · see citing works
Crystal, R. G. (1997) · Nature Medicine · doi:10.1038/nm0497-383 · Cited by 205 · see citing works
Inhibition of chemotaxis Ng-monomethyl-L-arginine: a role for cyclic GMP
Kaplan, S., Billiar, T. R., Curran, R., Zdziarski, U. E., Simmons, R. L., & Basford, R. (1989) · Blood · doi:10.1182/blood.v74.6.1885.1885 · Cited by 146 · see citing works
Roman, D. G., Dancis, A., Anderson, G. J., & Klausner, R. D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4342 · Cited by 128 · see citing works
Investigation of a role for reduction in ferric iron uptake by mouse duodenum
Raja, K. B., Simpson, R. J., & Peters, T. J. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90129-y · Cited by 124 · see citing works
Self-citationFerric reductases or flavin reductases?
Fontecave, M., Cov�s, J., & Pierre, J. (1994) · BioMetals · doi:10.1007/bf00205187 · Cited by 111 · see citing works
A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia
Huggenvik, J., Craven, C., Idzerda, R. L., Bernstein, S. I., Kaplan, J., & McKnight, G. S. (1989) · Blood · doi:10.1182/blood.v74.1.482.482 · Cited by 105 · see citing works
Riedel, H.-D., Remus, A. J., Fitscher, B. A., & Stremmel, W. (1995) · Biochemical Journal · doi:10.1042/bj3090745 · Cited by 90 · see citing works
Okuyama, E., Yamamoto, R., Ichikawa, Y., & Tsubaki, M. (1998) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(97)00216-1 · Cited by 68 · see citing works
Iron absorption by hypotransferrinaemic mice
Simpson, R. J., Lombard, M. G., Raja, K. B., Thatcher, R., & Peters, T. J. (1991) · British Journal of Haematology · doi:10.1111/j.1365-2141.1991.tb04490.x · Cited by 53 · see citing works
Self-citationStudies of Fe3+ transport across isolated intestinal brush-border membrane of the mouse
Simpson, R. J., & Peters, T. J. (1984) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(84)90047-6 · Cited by 47 · see citing works
Self-citationO'Riordan, D. K., Sharp, P., Sykes, R. M., Srai, S. K., Epstein, O., & Debnam, E. S. (1995) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1995.tb01950.x · Cited by 44 · see citing works
Dietary Iron Levels and Hypoxia Independently affect Iron Absorption in Mice
Simpson, R. J. (1996) · Journal of Nutrition · doi:10.1093/jn/126.7.1858 · Cited by 37 · see citing works
Self-citationKobayashi, K., Tsubaki, M., & Tagawa, S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.26.16038 · Cited by 35 · see citing works
Escriou, V., Laporte, F., Garin, J., Brandolin, G., & Vignais, P. V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36747-9 · Cited by 20 · see citing works
DeLeo, F. R., Olakanmi, O., Rasmussen, G. T., Lewis, T. S., McCormick, S. J., Nauseef, W. M., & Britigan, B. E. (1999) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(99)90208-1 · Cited by 7 · see citing works
Pountney, D. J., Raja, K. B., Simpson, R. J., & Wrigglesworth, J. M. (1999) · BioMetals · doi:10.1023/a:1009246912994 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Andrews, S. C., Robinson, A. K., & Rodríguez-Quiñones, F. (2003) · FEMS Microbiology Reviews · doi:10.1016/s0168-6445(03)00055-x · Cited by 2,702 · see citing works
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736 · see citing works
Mechanisms for copper acquisition, distribution and regulation
Kim, B., Nevitt, T., & Thiele, D. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.72 · Cited by 1,598 · see citing works
Copper homeostasis and cuproptosis in health and disease
Chen, L., Min, J., & Wang, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01229-y · Cited by 1,563 · see citing works
Zimmermann, M. B., & Hurrell, R. F. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61235-5 · Cited by 1,405 · see citing works
Biomarkers of Nutrition for Development—Folate Review
Bailey, L. B., Stover, P. J., McNulty, H., Fenech, M. F., Gregory, J. F., Mills, J. L., Pfeiffer, C. M., Fazili, Z., Zhang, M., Ueland, P. M., et al. (2015) · Journal of Nutrition · doi:10.3945/jn.114.206599 · Cited by 1,147 · see citing works
Papanikolaou, G., & Pantopoulos, K. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.06.021 · Cited by 1,070 · see citing works
Targeted Drug Delivery via the Transferrin Receptor-Mediated Endocytosis Pathway
Qian, Z., Li, H., Sun, H., & Ho, K. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.4.561 · Cited by 1,021 · see citing works
Iron homeostasis and oxidative stress: An intimate relationship
Galaris, D., Barbouti, A., & Pantopoulos, K. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118535 · Cited by 922 · see citing works
Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804 · see citing works
Mechanisms controlling cellular and systemic iron homeostasis
Galy, B., Conrad, M., & Muckenthaler, M. U. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00648-1 · Cited by 806 · see citing works
Ohgami, R. S., Campagna, D. R., Greer, E. L., Antiochos, B., McDonald, A., Chen, J., Sharp, J. J., Fujiwara, Y., Barker, J. E., & Fleming, M. D. (2005) · Nature Genetics · doi:10.1038/ng1658 · Cited by 775 · see citing works
Identification of an Intestinal Heme Transporter
Shayeghi, M., Latunde-Dada, G. O., Oakhill, J. S., Laftah, A. H., Takeuchi, K., Halliday, N., Khan, Y., Warley, A., McCann, F. E., Hider, R. C., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.025 · Cited by 755 · see citing works
Self-citationMuckenthaler, M. U., Galy, B., & Hentze, M. W. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155521 · Cited by 701 · see citing works
The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer
Kalinowski, D. S., & Richardson, D. R. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.4.2 · Cited by 721 · see citing works
MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study
Kuhl, C. K., Schrading, S., Bieling, H. B., Wardelmann, E., Leutner, C., Koenig, R., Kuhn, W. C., & Schild, H. H. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61232-x · Cited by 704 · see citing works
Non-transferrin bound iron: a key role in iron overload and iron toxicity
Brissot, P., Ropert, M., Le Lan, C., & Loréal, O. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.07.014 · Cited by 654 · see citing works
Andrews, N. C., & Schmidt, P. J. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.031905.164337 · Cited by 640 · see citing works
Current understanding of iron homeostasis
Anderson, G. J., & Frazer, D. M. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.155804 · Cited by 688 · see citing works
Forging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623 · see citing works
Heger, M., van Golen, R. F., Broekgaarden, M., & Michel, M. C. (2013) · Pharmacological Reviews · doi:10.1124/pr.110.004044 · Cited by 581 · see citing works
Phytate: impact on environment and human nutrition. A challenge for molecular breeding
Bohn, L., Meyer, A. S., & Rasmussen, S. K. (2008) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b0710640 · Cited by 577 · see citing works
Arredondo, M., & Núñez, M. T. (2005) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2005.07.010 · Cited by 550 · see citing works
Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury
Farina, M., Ávila, D. S., da Rocha, J. B. T., & Aschner, M. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.12.006 · Cited by 558 · see citing works
Labile iron pool: the main determinant of cellular response to oxidative stress
Kruszewski, M. K. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.004 · Cited by 529 · see citing works
Regulation of iron transport and the role of transferrin
Gkouvatsos, K., Papanikolaou, G., & Pantopoulos, K. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.10.013 · Cited by 518 · see citing works
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
Nutritive metal uptake in teleost fish
Bury, N. R., Walker, P., & Glover, C. N. (2002) · Journal of Experimental Biology · doi:10.1242/jeb.00068 · Cited by 522 · see citing works
The NRAMP family of metal-ion transporters
Nevo, Y., & Nelson, N. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.05.007 · Cited by 513 · see citing works
HIF-2α, but not HIF-1α, promotes iron absorption in mice
Mastrogiannaki, M., Matak, P., Keith, B., Simon, M. C., Vaulont, S., & Peyssonnaux, C. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38499 · Cited by 502 · see citing works
Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells
Crichton, R. R., Wilmet, S., Legssyer, R., & Ward, R. J. (2002) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(02)00461-0 · Cited by 494 · see citing works
Oudit, G. Y., Sun, H., Trivieri, M. G., Koch, S. E., Dawood, F., Ackerley, C., Yazdanpanah, M., Wilson, G. J., Schwartz, A., Liu, P. P., et al. (2003) · Nature Medicine · doi:10.1038/nm920 · Cited by 480 · see citing works
NEW INSIGHTS INTO ERYTHROPOIESIS: The Roles of Folate, Vitamin B 12 , and Iron
Koury, M. J., & Ponka, P. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132306 · Cited by 494 · see citing works
Viral infection and iron metabolism
Drakesmith, H., & Prentice, A. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1930 · Cited by 469 · see citing works
Overview of iron metabolism in health and disease
Dev, S., & Babitt, J. L. (2017) · Hemodialysis International · doi:10.1111/hdi.12542 · Cited by 469 · see citing works
Siderophores in Fungal Physiology and Virulence
Haas, H., Eisendle, M., & Turgeon, B. G. (2008) · Annual Review of Phytopathology · doi:10.1146/annurev.phyto.45.062806.094338 · Cited by 451 · see citing works
Shah, Y. M., Matsubara, T., Ito, S., Yim, S.-H., & Gonzalez, F. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.012 · Cited by 431 · see citing works
Brissot, P., Pietrangelo, A., Adams, P. C., de Graaff, B., McLaren, C. E., & Loréal, O. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.16 · Cited by 430 · see citing works
Cytokine-mediated regulation of iron transport in human monocytic cells
Ludwiczek, S., Aigner, E., Theurl, I., & Weiss, G. (2003) · Blood · doi:10.1182/blood-2002-08-2459 · Cited by 420 · see citing works
Iron Homeostasis and the Inflammatory Response
Wessling-Resnick, M. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104804 · Cited by 480 · see citing works
Cellular Consequences of Copper Complexes Used To Catalyze Bioorthogonal Click Reactions
Kennedy, D. C., McKay, C. S., Legault, M. C. B., Foss, D. V., Blake, J. A., Pegoraro, A. F., Stolow, A., Mester, Z., & Pezacki, J. P. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2083027 · Cited by 416 · see citing works
Mechanistic and regulatory aspects of intestinal iron absorption
Gulec, S., Anderson, G. J., & Collins, J. F. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00348.2013 · Cited by 406 · see citing works
Lane, D. J. R., Merlot, A. M., Huang, M. L.-H., Bae, D.-H., Jansson, P. J., Sahni, S., Kalinowski, D. S., & Richardson, D. R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.01.021 · Cited by 399 · see citing works
DMT1: A mammalian transporter for multiple metals
Garrick, M. D., Dolan, K. G., Horbinski, C., Ghio, A. J., Higgins, D. M., Porubcin, M., Moore, E., Hainsworth, L. N., Umbreit, J. N., Conrad, M. E., et al. (2003) · BioMetals · doi:10.1023/a:1020702213099 · Cited by 375 · see citing works
Jeong, S. Y., & David, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301988200 · Cited by 377 · see citing works
Liver iron sensing and body iron homeostasis
Wang, C.-Y., & Babitt, J. L. (2019) · Blood · doi:10.1182/blood-2018-06-815894 · Cited by 360 · see citing works
Stern, B. R., Solioz, M., Krewski, D. R., Aggett, P. J., Aw, T. C., Baker, S., Crump, K. S., Dourson, M. L., Haber, L. T., Hertzberg, R. C., et al. (2007) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937400600755911 · Cited by 373 · see citing works
Stoyanovsky, D. A., Tyurina, Y. Y., Shrivastava, I. H., Bahar, İ., Tyurin, V. A., Protchenko, O. V., Jadhav, S., Bolevich, S., Kozlov, A. V., Vladimirov, Y. A., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.008 · Cited by 374 · see citing works
Iron in infection and immunity
Nairz, M., & Weiss, G. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100864 · Cited by 359 · see citing works
Oxidative Stress and Iron Homeostasis: Mechanistic and Health Aspects
Galaris, D., & Pantopoulos, K. (2008) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360701713104 · Cited by 352 · see citing works
Metabolic crossroads of iron and copper
Collins, J. F., Prohaska, J. R., & Knutson, M. D. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00271.x · Cited by 352 · see citing works
Yanatori, I., & Kishi, F. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.07.020 · Cited by 360 · see citing works
Targeting iron metabolism in drug discovery and delivery
Crielaard, B. J., Lammers, T., & Rivella, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.248 · Cited by 352 · see citing works
Frazer, D. M., Wilkins, S. J., Becker, E., Vulpe, C. D., McKie, A. T., Trinder, D., & Anderson, G. J. (2002) · Gastroenterology · doi:10.1053/gast.2002.35353 · Cited by 342 · see citing works
Self-citationIron misregulation in the brain: a primary cause of neurodegenerative disorders
Ke, Y., & Qian, Z. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00353-3 · Cited by 339 · see citing works
Biomarkers of Nutrition for Development (BOND)—Iron Review
Lynch, S. R., Pfeiffer, C. M., Georgieff, M., Brittenham, G. M., Fairweather‐Tait, S. J., Hurrell, R. F., McArdle, H. J., & Raiten, D. J. (2018) · Journal of Nutrition · doi:10.1093/jn/nxx036 · Cited by 348 · see citing works
Gujja, P., Rosing, D. R., Tripodi, D. J., & Shizukuda, Y. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.083 · Cited by 328 · see citing works
Gut Microbiota and Iron: The Crucial Actors in Health and Disease
Yilmaz, B., & Li, H. (2018) · Pharmaceuticals · doi:10.3390/ph11040098 · Cited by 317 · see citing works
Nose, Y., Kim, B., & Thiele, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.009 · Cited by 321 · see citing works
Iron metabolism in the anemia of chronic disease
Weiss, G. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.006 · Cited by 322 · see citing works
Risks and benefits of copper in light of new insights of copper homeostasis
de Romaña, D. L., Olivares, M., Uauy, R. D., & Araya, M. (2011) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2010.11.004 · Cited by 322 · see citing works
Anderson, G. J., & Vulpe, C. D. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0051-1 · Cited by 317 · see citing works
Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans
Caza, M., & Kronstad, J. W. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00080 · Cited by 306 · see citing works
Mechanisms of Brain Iron Transport: Insight into Neurodegeneration and CNS Disorders
Mills, E., Dong, X.-P., Wang, F., & Xu, H. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.140 · Cited by 309 · see citing works
The Role of Iron Regulation in Immunometabolism and Immune-Related Disease
Cronin, S. J. F., Woolf, C. J., Weiss, G., & Penninger, J. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00116 · Cited by 299 · see citing works
Middendorp, S., Schneeberger, K., Wiegerinck, C. L., Mokrý, M., Akkerman, R. D. L., Wijngaarden, S., Clevers, H. C., & Nieuwenhuis, E. E. S. (2014) · Stem Cells · doi:10.1002/stem.1655 · Cited by 302 · see citing works
The physiological functions of iron regulatory proteins in iron homeostasis - an update
Zhang, D., Ghosh, M. C., & Rouault, T. A. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00124 · Cited by 301 · see citing works
An overview of molecular basis of iron metabolism regulation and the associated pathologies
Silva, B., & Faustino, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.011 · Cited by 300 · see citing works
Muckenthaler, M. U., Roy, C. N., Custodio, Á. O., Miñana, B., DEGRAAF, J., Montross, L. K., Andrews, N. C., & Hentze, M. W. (2003) · Nature Genetics · doi:10.1038/ng1152 · Cited by 293 · see citing works
Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones
Peeling, P., Dawson, B., Goodman, C., Landers, G., & Trinder, D. (2008) · European Journal of Applied Physiology · doi:10.1007/s00421-008-0726-6 · Cited by 292 · see citing works
Theil, E. C. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132212 · Cited by 291 · see citing works
Molecular control of vertebrate iron homeostasis by iron regulatory proteins
Wallander, M. L., Leibold, E. A., & Eisenstein, R. S. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.05.004 · Cited by 287 · see citing works
Transport of toxic metals by molecular mimicry.
Ballatori, N. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s5689 · Cited by 285 · see citing works
Iron and Alzheimer’s Disease: An Update on Emerging Mechanisms
Lane, D. J. R., Ayton, S., & Bush, A. I. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179944 · Cited by 278 · see citing works
Rouault, T. A., & Cooperman, S. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.08.002 · Cited by 280 · see citing works
Nichol, H., Law, J. H., & Winzerling, J. J. (2002) · Annual Review of Entomology · doi:10.1146/annurev.ento.47.091201.145237 · Cited by 279 · see citing works
Fleming, R. E., & Sly, W. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161296298 · Cited by 273 · see citing works
Substrate Profile and Metal-ion Selectivity of Human Divalent Metal-ion Transporter-1
Illing, A. C., Shawki, A., Cunningham, C. L., & Mackenzie, B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.364208 · Cited by 270 · see citing works
Divalent Metal Transporter 1 in Lead and Cadmium Transport
Bressler, J. P., Olivi, L., Cheong, J. H., Kim, Y., & BANNONA, D. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.011 · Cited by 272 · see citing works
P HYSIOLOGY AND M OLECULAR B IOLOGY OF D IETARY I RON A BSORPTION
Miret, S., Simpson, R. J., & McKie, A. T. (2003) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.23.011702.073139 · Cited by 269 · see citing works
Self-citationTaylor, M., Qu, A., Anderson, E. R., Matsubara, T., Martin, A., Gonzalez, F. J., & Shah, Y. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.03.007 · Cited by 265 · see citing works
The role of transporters in cellular heme and porphyrin homeostasis
Krishnamurthy, P. C., Xie, T., & Schuetz, J. D. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.02.001 · Cited by 260 · see citing works
Sequestration and scavenging of iron in infection
Parrow, N. L., Fleming, R. E., & Minnick, M. F. (2013) · Infection and Immunity · doi:10.1128/iai.00602-13 · Cited by 261 · see citing works
Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance
Wang, Y., Chen, Y., Zhang, J., Yang, Y., Fleishman, J. S., Wang, Y., Wang, J., Chen, J., Li, Y., & Wang, H. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.101018 · Cited by 265 · see citing works
Lane, D. J. R., & Richardson, D. R. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.007 · Cited by 264 · see citing works
Mechanisms of heme iron absorption: Current questions and controversies
West, A. R., & Oates, P. S. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4101 · Cited by 257 · see citing works
A precious metal: Iron, an essential nutrient for all cells
Cairo, G., Bernuzzi, F., & Recalcati, S. (2006) · Genes & Nutrition · doi:10.1007/bf02829934 · Cited by 252 · see citing works
A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders
Yiannikourides, A., & Latunde-Dada, G. O. (2019) · Medicines · doi:10.3390/medicines6030085 · Cited by 265 · see citing works
Self-citationThe Regulation of Iron Absorption and Homeostasis.
Wallace, D. F. (2016) · PubMed Central · Cited by 255 · see citing works
One ring to rule them all: Trafficking of heme and heme synthesis intermediates in the metazoans
Hamza, I., & Dailey, H. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.04.009 · Cited by 237 · see citing works
Brain iron metabolism: Neurobiology and neurochemistry
Ke, Y., & Qian, Z. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.07.009 · Cited by 236 · see citing works
The ins and outs of algal metal transport
Blaby, C., & Merchant, S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.04.010 · Cited by 237 · see citing works
The long history of iron in the Universe and in health and disease
Sheftel, A. D., Mason, A. B., & Ponka, P. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.002 · Cited by 234 · see citing works
The Metabolism of Neuronal Iron and Its Pathogenic Role in Neurological Disease: Review
Moos, T., & Morgan, E. H. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.002 · Cited by 234 · see citing works
Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells
Bannon, D. I., Abounader, R., Lees, P. S. J., & Bressler, J. P. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00184.2002 · Cited by 228 · see citing works
Modulation of iron transport proteins in human colorectal carcinogenesis
Brookes, M. J., Hughes, S., Turner, F. E., Reynolds, G., Sharma, N., Ismail, T., Berx, G., McKie, A. T., Hotchin, N., Anderson, G. J., et al. (2006) · Gut · doi:10.1136/gut.2006.094060 · Cited by 226 · see citing works
Self-citationNon-transferrin-bound iron transporters
Knutson, M. D. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.413 · Cited by 221 · see citing works
Anderson, E. R., & Shah, Y. M. (2012) · Comprehensive physiology · doi:10.1002/cphy.c120016 · Cited by 249 · see citing works
Lawen, A., & Lane, D. J. R. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4271 · Cited by 217 · see citing works
- Authors
- McKie, A. T., Barrow, D., Latunde-Dada, G. O., Rolfs, A., Sager, G., Mudaly, E., Mudaly, M., Richardson, C., Barlow, D., Bomford, A., Peters, T. J., Raja, K. B., Shirali, S., Hediger, M. A., Farzaneh, F., & Simpson, R. J.
- Affiliations
- King's College London (GB)
- Brigham and Women's Hospital (US)
- Department of Clinical Biochemistry,
- Corresponding author
- McKie, Andrew T.
- ORCID
- Venue
- Science
- Published
- 2001-03-02
- Volume
- 291
- Issue
- 5509
- Pages
- 1755-1759
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105749655
- Cited by
- 1,101
- References
- 26
- Citations by year
- 2026: 25 · 2025: 41 · 2024: 44 · 2023: 30 · 2022: 45 · 2021: 43 · 2020: 55 · 2019: 40 · 2018: 50 · 2017: 33 · 2016: 22 · 2015: 28 · 2014: 48 · 2013: 44 · 2012: 47
- FWCI
- 28.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- ferric reductase, dietary iron absorption, duodenal cytochrome b, Dcytb, cytochrome b561, brush border membrane, duodenal enterocytes, Xenopus oocyte expression
- MeSH terms
- Amino Acid Sequence, Anemia, Animals, Hypoxia, Cell Line, Cloning, Molecular, Cytochrome b Group, Duodenum, Enzyme Induction, Ferric Compounds, Intestinal Absorption, Intestinal Mucosa, Male, Microvilli, Molecular Sequence Data, Nitroblue Tetrazolium, Oocytes, Oxidation-Reduction, Oxidoreductases, RNA, Messenger, Tetrazolium Salts, Thiazoles, Transfection, Xenopus, Up-Regulation, DNA, Complementary, Iron, Dietary, Enterocytes, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
