Research Topics
Genomes and Genes | Matthias W HentzeSummaryAffiliation: European Molecular Biology Laboratory Country: Germany Publications
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Publications
Balancing acts: molecular control of mammalian iron metabolismMatthias W Hentze
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Cell 117:285-97. 2004..This has provided novel insights into gene regulation and unveiled remarkable links to the immune system...
Systems analysis of iron metabolism: the network of iron pools and fluxesTiago J S Lopes
Max Delbrueck Centrum of Molecular Medicine, Berlin Buch, Germany
BMC Syst Biol 4:112. 2010..Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole...- The IronChip evaluation package: a package of perl modules for robust analysis of custom microarraysYevhen Vainshtein
MMPU, Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
BMC Bioinformatics 11:112. 2010..The use of customized DNA microarrays improves overall data quality in many situations, however, only if for these specifically designed microarrays analysis tools are available... 
The REM phase of gene regulationMatthias W Hentze
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Trends Biochem Sci 35:423-6. 2010....- Two to tango: regulation of Mammalian iron metabolismMatthias W Hentze
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Cell 142:24-38. 2010..We also highlight some of the current questions in mammalian iron metabolism and discuss therapeutic opportunities arising from a better understanding of the underlying biological principles... - The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNAKent E Duncan
European Molecular Biology Laboratory, Heidelberg, Germany
Mol Cell 36:571-82. 2009..Our results uncover an important regulatory mechanism of Drosophila dosage compensation and provide insight into PABP-dependent translational control by 3' UTR-bound regulatory proteins... - Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)Bruno Galy
European Molecular Biology Laboratory, Heidelberg, Germany
Blood 106:2580-9. 2005..Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1... - A co-repressor assembly nucleated by Sex-lethal in the 3'UTR mediates translational control of Drosophila msl-2 mRNAMarica Grskovic
Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
EMBO J 22:5571-81. 2003..Our data support a model where dSXL binding to the 3'UTR of msl-2 mRNA activates the translational repressor domain, thereby enabling it to recruit co-repressors in a specific fashion... - Drosophila miR2 primarily targets the m7GpppN cap structure for translational repressionAgnieszka Zdanowicz
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany
Mol Cell 35:881-8. 2009.... - Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensationKent Duncan
Gene Expression Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
Genes Dev 20:368-79. 2006.... - A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in DrosophilaKarsten Beckmann
Gene Expression Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Cell 122:529-40. 2005..This failsafe mechanism thus forms the molecular basis of a critical step in dosage compensation. The results also elucidate a two step principle of translational control via multiple regulatory sites within an mRNA... - Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenumBruno Galy
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany
Cell Metab 7:79-85. 2008..IRPs are thus essential for intestinal function and organismal survival and coordinate the synthesis of key iron metabolism proteins in the duodenum... - Translational control via protein-regulated upstream open reading framesJan Medenbach
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Cell 145:902-13. 2011..We propose that protein-regulated uORFs constitute a systematic principle for the regulation of protein synthesis... - Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolismDunja Ferring-Appel
European Molecular Biology Laboratory, Heidelberg, Germany
Blood 113:679-87. 2009..This work defines the respective roles of IRP2 in the determination of critical body iron parameters such as organ iron loading and erythropoiesis... - Iron regulatory proteins secure mitochondrial iron sufficiency and functionBruno Galy
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Cell Metab 12:194-201. 2010..These results uncover a major role of the IRPs in cell biology: to ensure adequate iron supply to the mitochondrion for proper function of this critical organelle... - In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammationLydie Viatte
European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, 69117, Heidelberg, Germany
J Mol Med (Berl) 87:913-21. 2009..Our data indicate that the response of Irp1 (-/-) and Irp2 (-/-) mice to acute local inflammation is largely preserved... - Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosisMartina Muckenthaler
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Nat Genet 34:102-7. 2003..We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1... - Mechanism of translational regulation by miR-2 from sites in the 5' untranslated region or the open reading frameFrancesca Moretti
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
RNA 16:2493-502. 2010..Using single or dual binding sites, it also reveals a biological rationale for the high prevalence of miR regulatory sites in the 3'UTR... - Generation of conditional alleles of the murine Iron Regulatory Protein (IRP)-1 and -2 genesBruno Galy
European Molecular Biology Laboratory, Heidelberg, Germany
Genesis 43:181-8. 2005..If not removed, the gene trap construct causes partially penetrant embryonic lethality unrelated to IRP deficiency when inserted within the Irp1 but not the Irp2 locus. We discuss the implications for functional genomics in the mouse... - Iron regulation and the cell cycle: identification of an iron-responsive element in the 3'-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategyMayka Sanchez
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
J Biol Chem 281:22865-74. 2006..This work describes a new experimental strategy to explore the IRE/IRP regulatory network and uncovers a previously unrecognized regulatory link between iron metabolism and the cell cycle... - Bruno acts as a dual repressor of oskar translation, promoting mRNA oligomerization and formation of silencing particlesMarina Chekulaeva
Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Cell 124:521-33. 2006..Bruno-dependent mRNA oligomerization into silencing particles emerges as a mode of translational control that may be particularly suited to coupling with mRNA transport... - Molecular analysis of iron overload in beta2-microglobulin-deficient miceMartina U Muckenthaler
European Molecular Biology Laboratory, D 69117, Heidelberg, Germany
Blood Cells Mol Dis 33:125-31. 2004.... - PABP and the poly(A) tail augment microRNA repression by facilitated miRISC bindingFrancesca Moretti
European Molecular Biology Laboratory, Heidelberg, Germany
Nat Struct Mol Biol 19:603-8. 2012..We integrated these data into a revised model for the function of PABP and the poly(A) tail in miRNA-mediated translational repression... - Drosophila miR2 induces pseudo-polysomes and inhibits translation initiationRolf Thermann
European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Nature 447:875-8. 2007..These results directly show the inhibition of m7GpppG cap-mediated translation initiation as the mechanism of miR2 function, and uncover pseudo-polysomal messenger ribonucleoprotein assemblies that may help to explain earlier findings... - SIREs: searching for iron-responsive elementsMonica Campillos
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Nucleic Acids Res 38:W360-7. 2010..The SIREs (Search for iron-responsive elements) web server is freely available on the web at http://ccbg.imppc.org/sires/index.html... - Translation initiation by the c-myc mRNA internal ribosome entry sequence and the poly(A) tailChristian Thoma
European Molecular Biology Laboratory EMBL, 69117 Heidelberg, Germany
RNA 14:1579-89. 2008..The mechanistic distinctions from cap-dependent translation may allow specific translational control of the c-myc mRNA and possibly other cellular mRNAs that initiate translation via IRESs... - Enhancement of IRES-mediated translation of the c-myc and BiP mRNAs by the poly(A) tail is independent of intact eIF4G and PABPChristian Thoma
EMBL Heidelberg, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Mol Cell 15:925-35. 2004..The polyadenylated mRNA translation from cellular IRESs is also profoundly sensitive to eIF4A activity in vitro. These mechanistic and molecular distinctions implicate the potential for a new layer of translational control mechanisms... - Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shockThomas Preiss
EMBL Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Nat Struct Biol 10:1039-47. 2003..Thus, signal-induced changes in the transcriptome are amplified at the translational level. These results unveil a higher level of coordinated gene regulation that we refer to as 'potentiation.'.. - A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domainSusanne Till
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Nat Struct Mol Biol 14:897-903. 2007..Proteins containing the conserved Ago hook may thus be important regulatory components of effector complexes in RNA interference... - Internal ribosome entry sequence-mediated translation initiation triggers nonsense-mediated decayJill A Holbrook
European Molecular Biology Laboratory, University Hospital Heidelberg, Molecular Medicine Partnership Unit, University of Heidelberg, Im Neuenheimer Feld 150, Heidelberg 69120, Germany
EMBO Rep 7:722-6. 2006..These data generalize the previous model and suggest that translation per se, irrespective of how it is initiated, can mediate NMD... - Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translationPatrick Hundsdoerfer
Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Proc Natl Acad Sci U S A 102:13421-6. 2005.... - Iron regulatory proteins control a mucosal block to intestinal iron absorptionBruno Galy
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany
Cell Rep 3:844-57. 2013..IRPs thus secure sufficient iron transport across absorptive enterocytes by restricting the ferritin "mucosal block" and define a basal set point for iron absorption upon which IRP-independent systemic regulatory inputs are overlaid... - Targeted mutagenesis of the murine IRP1 and IRP2 genes reveals context-dependent RNA processing differences in vivoBruno Galy
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
RNA 10:1019-25. 2004..We discuss the implications for the understanding of RNA processing and for targeting strategies for functional genomics in the mouse... - Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNAFátima Gebauer
European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Mol Cell 11:1397-404. 2003..These results elucidate a critical regulatory step for dosage compensation in Drosophila melanogaster... - The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeastJulie Baron-Benhamou
Gene Expression Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
RNA 9:654-62. 2003.... - Insights into RNA biology from an atlas of mammalian mRNA-binding proteinsAlfredo Castello
European Molecular Biology Laboratory, Heidelberg, Germany
Cell 149:1393-406. 2012..Interactome capture is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings... - Relationships and distinctions in iron-regulatory networks responding to interrelated signalsMartina Muckenthaler
European Molecular Biology Laboratory, Heidelberg, Germany
Blood 101:3690-8. 2003..These findings also demonstrate the broad utility of gene-expression profiling with the IronChip to study iron metabolism and related human diseases... - An efficient factor-depleted mammalian in vitro translation systemAurelie M Rakotondrafara
European Molecular Biology Laboratory, Heidelberg, Germany
Nat Protoc 6:563-71. 2011..The complete procedure can normally be conducted within 1 week and carried out in parallel for multiple (candidate) factors... - Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular functionNadia Hubert
European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
Proc Natl Acad Sci U S A 99:12345-50. 2002..These results uncover an unexpected complexity of DMT1 expression and regulation, with implications for understanding the physiology, cell biology, and pathophysiology of mammalian iron metabolism... - Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cellsThomas Schell
European Molecular Biology Laboratory Heidelberg, Gene Expression Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Biochem J 373:775-83. 2003..Components of the exon-exon junction complex or the translational eukaryotic release factor (eRF) 3 were not identified in complexes associated with Hupf1-2tag. We discuss these findings in the context of current models of NMD... - Expression of the subgenomic hepatitis C virus replicon alters iron homeostasis in Huh7 cellsCarine Fillebeen
Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, Que, Canada H3T 1E2
J Hepatol 47:12-22. 2007..To seek for molecular links, we employed an established cell culture model for viral replication, and assessed how the expression of an HCV subgenomic replicon affects iron metabolism in host Huh7 hepatoma cells... - Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiencyMayka Sanchez
Molecular Medicine Partnership Unit, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
Nat Struct Mol Biol 14:420-6. 2007..They also show that an IRE that is structurally distinct from, for example, the ferritin mRNA IRE and that has been missed by in silico approaches, can mediate mechanistically similar responses... - Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stressKhristy Thompson
Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
J Neurosci Res 71:46-63. 2003..These results suggest that this mouse may be a model to determine the role of iron mismanagement in neurodegenerative disorders and for testing antioxidant therapeutic strategies... - Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory networkMartina U Muckenthaler
Molecular Medicine Partnership Unit, Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D 69120 Heidelberg, Germany
Annu Rev Nutr 28:197-213. 2008..We also discuss how the IRE/IRP regulatory system communicates with the hepcidin/ferroportin system to connect the control networks for systemic and cellular iron balance... - Hfe acts in hepatocytes to prevent hemochromatosisMaja Vujic Spasic
Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
Cell Metab 7:173-8. 2008..This work demonstrates that local Hfe expression in hepatocytes serves to maintain physiological iron homeostasis, answering a long-standing question in medicine and explaining earlier clinical observations... - Expression of epithelial cell iron-related genes upon infection by Neisseria meningitidisRobert A Bonnah
Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Portland, OR, USA
Cell Microbiol 6:473-84. 2004..This finding suggests that low IRP activity may be responsible in part for the decrease in TfR-1 mRNA levels. A discussion of these novel findings in relation to MC infection and virulence is provided... - Nonsense-mediated mRNA decay: from vacuum cleaner to Swiss army knifeGabriele Neu-Yilik
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
Genome Biol 5:218. 2004..Two new approaches have identified physiological NMD substrates, and suggest that NMD functions as a multipurpose tool in the modulation of gene expression... - Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activityJian Wang
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada
Mol Cell Biol 24:954-65. 2004..Our results challenge the current model for IRP2 regulation and provide direct pharmacological evidence for the involvement of 2-oxoglutarate-dependent oxygenases in a pathway for IRP2 degradation... - Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportinThomas Herrmann
Department of Internal Medicine IV, University of Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany
J Mol Med (Berl) 82:39-48. 2004..Rather, the duodenal ferric reductase Dcytb may act as a possible mediator of iron overload in Hfe deficiency... - Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirementsNiels H Gehring
Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg 69120, Germany
Mol Cell 20:65-75. 2005..These results are integrated into a nonlinear model for mammalian NMD involving alternative routes of entry that converge at a common requirement of UPF1... - An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in miceCindy N Roy
Children s Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Genet 36:481-5. 2004..These data suggest a previously unidentified role for Hfe in innate immunity and ACD... - Abnormally spliced beta-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decaySven Danckwardt
Department of General Pediatrics, Charit, Humboldt-University, Berlin, Germany
Blood 99:1811-6. 2002..It can therefore serve as a useful tool for defining the mechanisms that permit specific transcripts to circumvent the NMD pathway... - Nonsense-mediated decay approaches the clinicJill A Holbrook
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D-69120 Heidelberg, Germany
Nat Genet 36:801-8. 2004..Potential 'NMD therapeutics' will therefore need to strike a balance between the general physiological benefits of NMD and its detrimental effects in cases of specific genetic mutations... - A chemiluminescence-based reporter system to monitor nonsense-mediated mRNA decayStephanie Boelz
Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
Biochem Biophys Res Commun 349:186-91. 2006..Wortmannin treatment enhanced NMD reporter expression in our system in a dose-dependent way, illustrating its utility for small molecule screening... - Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouseBruno Galy
Nat Genet 38:967-9; discussion 969-70. 2006 - STAT3 mediates hepatic hepcidin expression and its inflammatory stimulationMaria Vittoria Verga Falzacappa
Molecular Medicine Partnership Unit, University of Heidelberg, Heidelberg, Germany
Blood 109:353-8. 2007..These results identify a missing link in the acute-phase activation of hepcidin and establish STAT3 as a key effector of baseline hepcidin expression and during inflammatory conditions... - Physiologic systemic iron metabolism in mice deficient for duodenal HfeMaja Vujic Spasic
Molecular Medicine Partnership Unit, University of Heidelberg, Germany
Blood 109:4511-7. 2007.... - Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1Susanne Ludwiczek
Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, Anichstr 35, A 6020 Innsbruck, Austria
Nat Med 13:448-54. 2007..Modulation of DMT-1 function by L-type calcium channel blockers emerges as a new pharmacological therapy for the treatment of iron overload disorders... - Complex translational regulation of BACE1 involves upstream AUGs and stimulatory elements within the 5' untranslated regionMarija Mihailovich
San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Nucleic Acids Res 35:2975-85. 2007..Furthermore, we have evidence that a sequence within the region 222-323 of the BACE1 5' UTR has a stimulatory effect on translation that might depend on the presence of trans-acting factors... - The uORF-containing thrombopoietin mRNA escapes nonsense-mediated decay (NMD)Clemens Stockklausner
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, 69120 Heidelberg, Germany
Nucleic Acids Res 34:2355-63. 2006..Thus, regulation of TPO expression is independent of NMD, implying that mRNAs bearing uORFs cannot generally be considered to represent NMD targets... - The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathwayMarcelo H Viegas
Department of Pediatric Oncology, Hematology and Immunology, Children s Hospital, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
Nucleic Acids Res 35:4542-51. 2007..We conclude that cellular concentrations of RNPS1 can modify NMD efficiency and propose that cell type specific co-factor availability represents a novel principle that controls NMD... - Is congenital secondary erythrocytosis/polycythemia caused by activating mutations within the HIF-2 alpha iron-responsive element?Melanie J Percy
Blood 110:2776-7. 2007 - The molecular circuitry regulating the switch between iron deficiency and overload in miceHenry Mok
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 281:7946-51. 2006..We conclude that regulatory alleles, such as Pcm, with highly dynamic changes in iron balance are ideally suited to interrogate the genetic circuitry regulating iron metabolism... - Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C VirusCarine Fillebeen
Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, 3755 Cote Sainte Catherine Road, Montreal, Quebec H3T 1E2, Canada
J Biol Chem 280:9049-57. 2005..Our data provide a direct molecular link between iron and HCV replication... - Molecular mechanisms of translational controlFátima Gebauer
Centre de Regulacio Genomica, Passeig Maritim 37 49, 08003 Barcelona, Spain
Nat Rev Mol Cell Biol 5:827-35. 2004..Instead of providing a comprehensive account of the examples that are known at present, we discuss instructive cases that serve as paradigms for different modes of translational control... - IRP1-independent alterations of cardiac iron metabolism in doxorubicin-treated miceGianfranca Corna
Institute of General Pathology, University of Milan, Via Mangiagalli 31, Milan 20133, Italy
J Mol Med 84:551-60. 2006..The observed IRP2 downmodulation could serve as a means to counteract DOX cardiotoxicity by reducing the "free" cellular iron pool...