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• W2587806613 abstract "Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe4S4]2+ clusters and low-spin FeII hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE−/− mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE−/− livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2−/− hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin FeII ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe4S4]2+ clusters and low-spin FeII hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE−/− mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE−/− livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2−/− hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin FeII ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. From an early stage of fetal development until the end of life, the heart functions unceasingly to pump blood throughout the body. This requires a high and sustained level of metabolic energy unrivaled by any other organ except perhaps the brain. Mitochondria, the organelle responsible for generating most of the chemical energy in cells, serve a critical role in cardiac function. Improving our understanding of cardiac physiology is important because heart disease is the most common cause of death in the Western world (1.Sanchis-Gomar F. Perez-Quilis C. Leischik R. Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome.Ann. Transl. Med. 2016; 4: 256Crossref PubMed Scopus (626) Google Scholar). The preponderance of iron-containing centers in respiration-related mitochondrial proteins makes this metal a major player in cardiac physiology. Much of the iron that enters cardiomyocytes is used to build iron-sulfur clusters (ISCs) 3The abbreviations used are: ISCiron-sulfur clusterBDblood doubletΔEQquadrupole splittingFAFriedreich ataxiaHFEhigh iron geneHFE−/−genotype in which both alleles of the HFE gene have been mutatedHHhereditary hemochromatosisICP-MSinductively coupled plasma mass spectrometryIREiron responsive elementIRP1/2iron responsive element proteins 1 and 2IRP2−/−genotype in which both alleles of the IRP2 gene have been mutatedMBMössbauerNHHSnonheme high-spinROSreactive oxygen speciesTfR1transferrin receptor 1mt-ferritinmitochondrial ferritin. and heme centers many of which are installed into mitochondrial respiratory complexes and respiration-related proteins. Excess cellular iron is generally stored within the core of cytosolic ferritin, a spherically shaped protein complex composed of variable ratios of H- and L-subunits (2.Theil E.C. Tosha T. Behera R.K. Solving biology's iron chemistry problem with ferritin nanocages.Acc. Chem. Res. 2016; 49: 784-791Crossref PubMed Scopus (59) Google Scholar). H-ferritin is especially important in cardiac function (3.Ferreira C. Bucchini D. Martin M.E. Levi S. Arosio P. Grandchamp B. Beaumont C. Early embryonic lethality of H ferritin gene deletion in mice.J. Biol. Chem. 2000; 275: 3021-3024Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar, 4.Ahmad S. Moriconi F. Naz N. Sultan S. Sheikh N. Ramadori G. Malik I.A. Ferritin L and ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions.Int. J. Clin. Exp. Pathol. 2013; 6: 622-629PubMed Google Scholar). Besides storing iron, H-ferritin helps cells manage the metal (5.Kistler M. Even A. Wagner S. Becker C. Darshan D. Vanoaica L. Kühn L.C. Schümann K. Fe-59-distribution in conditional ferritin-H-deleted mice.Exp. Hematol. 2014; 42: 59-69Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar). H-ferritin levels are significantly lower in mice hearts after a myocardial infarct (6.Omiya S. Hikoso S. Imanishi Y. Saito A. Yamaguchi O. Takeda T. Mizote I. Oka T. Taneike M. Nakano Y. Matsumura Y. Nishida K. Sawa Y. Hori M. Otsu K. Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes.J. Mol. Cell. Cardiol. 2009; 46: 59-66Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). Such hearts contain spotty iron deposits and suffer from excessive oxidative stress. Deleting H-ferritin reduces the viability of cardiomyocytes and increases these deposits (6.Omiya S. Hikoso S. Imanishi Y. Saito A. Yamaguchi O. Takeda T. Mizote I. Oka T. Taneike M. Nakano Y. Matsumura Y. Nishida K. Sawa Y. Hori M. Otsu K. Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes.J. Mol. Cell. Cardiol. 2009; 46: 59-66Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). Excessive iron and increased oxidative stress damage cardiomyocytes and contribute to heart failure (6.Omiya S. Hikoso S. Imanishi Y. Saito A. Yamaguchi O. Takeda T. Mizote I. Oka T. Taneike M. Nakano Y. Matsumura Y. Nishida K. Sawa Y. Hori M. Otsu K. Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes.J. Mol. Cell. Cardiol. 2009; 46: 59-66Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). Mitochondrial ferritin (mt-ferritin) is highly expressed in heart mitochondria (7.Santambrogio P. Biasiotto G. Sanvito F. Olivieri S. Arosio P. Levi S. Mitochondrial ferritin expression in adult mouse tissues.J. Histochem. Cytochem. 2007; 55: 1129-1137Crossref PubMed Scopus (122) Google Scholar). It functions to sequester FeII in mitochondria and thus protect the organelle from iron-dependent oxidative damage (8.Campanella A. Rovelli E. Santambrogio P. Cozzi A. Taroni F. Levi S. Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia.Hum. Mol. Genet. 2009; 18: 1-11Crossref PubMed Scopus (116) Google Scholar). iron-sulfur cluster blood doublet quadrupole splitting Friedreich ataxia high iron gene genotype in which both alleles of the HFE gene have been mutated hereditary hemochromatosis inductively coupled plasma mass spectrometry iron responsive element iron responsive element proteins 1 and 2 genotype in which both alleles of the IRP2 gene have been mutated Mössbauer nonheme high-spin reactive oxygen species transferrin receptor 1 mitochondrial ferritin. Cardiomyopathy is common in iron-overload diseases such as hereditary hemochromatosis (HH) (9.Kohgo Y. Ikuta K. Ohtake T. Torimoto Y. Kato J. Body iron metabolism and pathophysiology of iron overload.Int. J. Hematol. 2008; 88: 7-15Crossref PubMed Scopus (397) Google Scholar). HH initially impacts the liver, but eventually affects the heart, causing ROS damage especially to mitochondria (10.Nam H. Wang C.Y. Zhang L. Zhang W. Hojyo S. Fukada T. Knutson M.D. ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders.Haematologica. 2013; 98: 1049-1057Crossref PubMed Scopus (121) Google Scholar, 11.Chua-anusorn W. Tran K.C. Webb J. Macey D.J. St. Pierre T.G. Chemical speciation of iron deposits in thalassemic heart tissue.Inorg. Chim. Acta. 2000; 300: 932-936Crossref Scopus (10) Google Scholar, 12.Neves J.V. Olsson I.A. Porto G. Rodrigues P.N. Hemochromatosis and pregnancy: iron stores in the HFE−/− mouse are not reduced by multiple pregnancies.Am. J. Physiol. Gastrointest. Liver Physiol. 2010; 298: G525-G529Crossref PubMed Scopus (7) Google Scholar). The most common cause of HH is a mutation in the HFE gene. HFE−/− mutant livers contain 4–6 times more iron than controls, whereas the iron content of mutant hearts is slightly elevated (13.Gutiérrez L. Quintana C. Patiño C. Bueno J. Coppin H. Roth M.P. Lázaro F.J. Iron speciation study in HFE knockout mice tissues: magnetic and ultrastructural characterization.Biochim. Biophys. Acta. 2009; 1792: 541-547Crossref PubMed Scopus (23) Google Scholar, 14.Subramaniam V.N. McDonald C.J. Ostini L. Lusby P.E. Wockner L.F. Ramm G.A. Wallace D.F. Hepatic iron deposition does not predict iron loading in mouse models of hereditary hemochromatosis.Am. J. Pathol. 2012; 181: 1173-1179Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar). Hemosiderin, a poorly defined iron-loaded breakdown product of ferritin (15.St. Pierre T.G. Tran K.C. Webb J. Macey D.J. Pootrakul P. Dickson D.P. Core structures of haemosiderins deposited in various organs in β-thalassemia hemoglobin E disease.Hyperfine Interact. 1992; 71: 1279-1282Crossref Scopus (26) Google Scholar), accumulates along with ferritin in mutant livers but not in mutant hearts (13.Gutiérrez L. Quintana C. Patiño C. Bueno J. Coppin H. Roth M.P. Lázaro F.J. Iron speciation study in HFE knockout mice tissues: magnetic and ultrastructural characterization.Biochim. Biophys. Acta. 2009; 1792: 541-547Crossref PubMed Scopus (23) Google Scholar, 14.Subramaniam V.N. McDonald C.J. Ostini L. Lusby P.E. Wockner L.F. Ramm G.A. Wallace D.F. Hepatic iron deposition does not predict iron loading in mouse models of hereditary hemochromatosis.Am. J. Pathol. 2012; 181: 1173-1179Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar). Hemosiderin is found in some iron-overloaded organs (15.St. Pierre T.G. Tran K.C. Webb J. Macey D.J. Pootrakul P. Dickson D.P. Core structures of haemosiderins deposited in various organs in β-thalassemia hemoglobin E disease.Hyperfine Interact. 1992; 71: 1279-1282Crossref Scopus (26) Google Scholar, 16.Bell S.H. Weir M.P. Dickson D.P. Gibson J.F. Sharp G.A. Peters T.J. Mössbauer spectroscopic studies of human haemosiderin and ferritin.Biochim. Biophys. Acta. 1984; 787: 227-236Crossref PubMed Scopus (142) Google Scholar, 17.Webb J. Macey D.J. Chua-anusorn W. St. Pierre T.G. Brooker L.R. Rahman I. Noller B. Iron biominerals in medicine and the environment.Coord. Chem. Rev. 1999; 190–192: 1199-1215Crossref Scopus (19) Google Scholar). Mössbauer (MB) spectroscopy has been used to investigate the iron content of hearts from patients with β-thalassemia, another iron-overload blood disease (18.St Pierre T.G. Tran K.C. Webb J. Macey D.J. Heywood B.R. Sparks N.H. Wade V.J. Mann S. Pootrakul P. Organ-specific crystalline structures of ferritin cores in β-thalassemia hemoglobin E.Biol. Met. 1991; 4: 162-165Crossref PubMed Scopus (43) Google Scholar, 19.Kaufman K.S. Papaefthymiou G.C. Frankel R.B. Rosenthal A. Nature of iron deposits on the cardiac walls in β-thalassemia by Mössbauer spectroscopy.Biochim. Biophys. Acta. 1980; 629: 522-529Crossref PubMed Scopus (33) Google Scholar, 20.Perdomini M. Belbellaa B. Monassier L. Reutenauer L. Messaddeq N. Cartier N. Crystal R.G. Aubourg P. Puccio H. Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia.Nat. Med. 2014; 20: 542-547Crossref PubMed Scopus (142) Google Scholar). The average iron concentration in the β-thalassemia heart is nearly 3 times higher than normal (11.Chua-anusorn W. Tran K.C. Webb J. Macey D.J. St. Pierre T.G. Chemical speciation of iron deposits in thalassemic heart tissue.Inorg. Chim. Acta. 2000; 300: 932-936Crossref Scopus (10) Google Scholar). MB spectra of β-thalassemia heart tissue exhibit features of ferritin, a high-spin FeIII species, and perhaps hemosiderin (11.Chua-anusorn W. Tran K.C. Webb J. Macey D.J. St. Pierre T.G. Chemical speciation of iron deposits in thalassemic heart tissue.Inorg. Chim. Acta. 2000; 300: 932-936Crossref Scopus (10) Google Scholar, 18.St Pierre T.G. Tran K.C. Webb J. Macey D.J. Heywood B.R. Sparks N.H. Wade V.J. Mann S. Pootrakul P. Organ-specific crystalline structures of ferritin cores in β-thalassemia hemoglobin E.Biol. Met. 1991; 4: 162-165Crossref PubMed Scopus (43) Google Scholar). The control MB spectrum was too noisy to evaluate because the heart was neither overloaded nor enriched in 57Fe. Individuals with Friedreich's ataxia (FA) develop cardiomyopathy in conjunction with mitochondrial iron accumulation and ROS damage (21.Michael S. Petrocine S.V. Qian J. Lamarche J.B. Knutson M.D. Garrick M.D. Koeppen A.H. Iron and iron-responsive proteins in the cardiomyopathy of Friedreich's ataxia.Cerebellum. 2006; 5: 257-267Crossref PubMed Scopus (104) Google Scholar, 22.Payne R.M. The heart in Friedreich's ataxia: basic findings and clinical implications.Prog Pediatr. Cardiol. 2011; 31: 103-109Crossref PubMed Scopus (31) Google Scholar). FA arises from a deficiency in frataxin, a mitochondrial protein involved in ISC assembly (23.Whitnall M. Suryo Rahmanto Y. Huang M.L. Saletta F. Lok H.C. Gutiérrez L. Lázaro F.J. Fleming A.J. St Pierre T.G. Mikhael M.R. Ponka P. Richardson D.R. Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.Proc. Natl. Acad. Sci. U.S.A.,. 2012; 109: 20590-20595Crossref PubMed Scopus (77) Google Scholar). Eighty percent of FA patients die of cardiac disease (24.Pousset F. Legrand L. Monin M.L. Ewenczyk C. Charles P. Komajda M. Brice A. Pandolfo M. Isnard R. Tezenas du Montcel S. Durr A. A 22-year follow-up study of long-term cardiac outcome and predictors of survival in Friedreich ataxia.JAMA Neurol. 2015; 72: 1334-1341Crossref PubMed Scopus (50) Google Scholar). Mice in which frataxin was deleted in cardiac muscle exhibited the classical progression of FA (20.Perdomini M. Belbellaa B. Monassier L. Reutenauer L. Messaddeq N. Cartier N. Crystal R.G. Aubourg P. Puccio H. Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia.Nat. Med. 2014; 20: 542-547Crossref PubMed Scopus (142) Google Scholar, 24.Pousset F. Legrand L. Monin M.L. Ewenczyk C. Charles P. Komajda M. Brice A. Pandolfo M. Isnard R. Tezenas du Montcel S. Durr A. A 22-year follow-up study of long-term cardiac outcome and predictors of survival in Friedreich ataxia.JAMA Neurol. 2015; 72: 1334-1341Crossref PubMed Scopus (50) Google Scholar, 25.Whitnall M. Suryo Rahmanto Y. Sutak R. Xu X. Becker E.M. Mikhael M.R. Ponka P. Richardson D.R. The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation.Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 9757-9762Crossref PubMed Scopus (101) Google Scholar, 26.Puccio H. Simon D. Cossée M. Criqui-Filipe P. Tiziano F. Melki J. Hindelang C. Matyas R. Rustin P. Koenig M. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits.Nat. Genet. 2001; 27: 181-186Crossref PubMed Scopus (598) Google Scholar). At 7 weeks, mutant mice became deficient in ISCs, and at 9 weeks, the iron concentration in mutant hearts increased and respiratory activity declined (27.Sutak R. Xu X. Whitnall M. Kashem M.A. Vyoral D. Richardson D.R. Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism.Proteomics. 2008; 8: 1731-1741Crossref PubMed Scopus (34) Google Scholar). At 10 weeks, the concentration of iron in mutant hearts contained nearly 10 times more iron than WT hearts, which contained about 1.3 mm iron (26.Puccio H. Simon D. Cossée M. Criqui-Filipe P. Tiziano F. Melki J. Hindelang C. Matyas R. Rustin P. Koenig M. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits.Nat. Genet. 2001; 27: 181-186Crossref PubMed Scopus (598) Google Scholar, 28.Zhao N. Sun Z. Mao Y. Hang P. Jiang X. Sun L. Zhao J. Du Z. Myocardial iron metabolism in the regulation of cardiovascular diseases in rats.Cell. Physiol. Biochem. 2010; 25: 587-594Crossref PubMed Scopus (22) Google Scholar). The excess iron in the mutant cells flowed into mitochondria where it aggregated and generated ROS (23.Whitnall M. Suryo Rahmanto Y. Huang M.L. Saletta F. Lok H.C. Gutiérrez L. Lázaro F.J. Fleming A.J. St Pierre T.G. Mikhael M.R. Ponka P. Richardson D.R. Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.Proc. Natl. Acad. Sci. U.S.A.,. 2012; 109: 20590-20595Crossref PubMed Scopus (77) Google Scholar, 25.Whitnall M. Suryo Rahmanto Y. Sutak R. Xu X. Becker E.M. Mikhael M.R. Ponka P. Richardson D.R. The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation.Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 9757-9762Crossref PubMed Scopus (101) Google Scholar, 27.Sutak R. Xu X. Whitnall M. Kashem M.A. Vyoral D. Richardson D.R. Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism.Proteomics. 2008; 8: 1731-1741Crossref PubMed Scopus (34) Google Scholar, 29.Huang M.L. Becker E.M. Whitnall M. Suryo Rahmanto Y. Ponka P. Richardson D.R. Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant.Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 16381-16386Crossref PubMed Scopus (172) Google Scholar). MB spectroscopy was used to characterize the iron aggregates in hearts of 9-week frataxin KO mice (23.Whitnall M. Suryo Rahmanto Y. Huang M.L. Saletta F. Lok H.C. Gutiérrez L. Lázaro F.J. Fleming A.J. St Pierre T.G. Mikhael M.R. Ponka P. Richardson D.R. Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.Proc. Natl. Acad. Sci. U.S.A.,. 2012; 109: 20590-20595Crossref PubMed Scopus (77) Google Scholar). The spectrum was noisy because mice were not enriched in 57Fe. It exhibited a single quadrupole doublet due to FeIII oxyhydroxide nanoparticles (23.Whitnall M. Suryo Rahmanto Y. Huang M.L. Saletta F. Lok H.C. Gutiérrez L. Lázaro F.J. Fleming A.J. St Pierre T.G. Mikhael M.R. Ponka P. Richardson D.R. Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.Proc. Natl. Acad. Sci. U.S.A.,. 2012; 109: 20590-20595Crossref PubMed Scopus (77) Google Scholar). The low-temperature MB spectrum of the liver from the same frataxin KO mice was dominated by a sextet due to ferritin (11.Chua-anusorn W. Tran K.C. Webb J. Macey D.J. St. Pierre T.G. Chemical speciation of iron deposits in thalassemic heart tissue.Inorg. Chim. Acta. 2000; 300: 932-936Crossref Scopus (10) Google Scholar, 23.Whitnall M. Suryo Rahmanto Y. Huang M.L. Saletta F. Lok H.C. Gutiérrez L. Lázaro F.J. Fleming A.J. St Pierre T.G. Mikhael M.R. Ponka P. Richardson D.R. Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.Proc. Natl. Acad. Sci. U.S.A.,. 2012; 109: 20590-20595Crossref PubMed Scopus (77) Google Scholar). Cardiac failure is the most prevalent cause of death in the elderly and is commonly associated with impaired energy homeostasis (30.Schulz T.J. Westermann D. Isken F. Voigt A. Laube B. Thierbach R. Kuhlow D. Zarse K. Schomburg L. Pfeiffer A.F. Tschöpe C. Ristow M. Activation of mitochondrial energy metabolism protects against cardiac failure.Aging. 2010; 2: 843-853Crossref PubMed Scopus (48) Google Scholar, 31.Elas M. Bielanska J. Pustelny K. Plonka P.M. Drelicharz L. Skorka T. Tyrankiewicz U. Wozniak M. Heinze-Paluchowska S. Walski M. Wojnar L. Fortin D. Ventura-Clapier R. Chlopicki S. Detection of mitochondrial dysfunction by EPR technique in mouse model of dilated cardiomyopathy.Free Rad. Biol. Med. 2008; 45: 321-328Crossref PubMed Scopus (42) Google Scholar). Aged mitochondria often have respiratory defects (32.Lesnefsky E.J. Gudz T.I. Migita C.T. Ikeda-Saito M. Hassan M.O. Turkaly P.J. Hoppel C.L. Ischemic injury to mitochondrial electron transport in the aging heart: damage to the iron-sulfur protein subunit of electron transport complex III.Arch. Biochem. Biophys. 2001; 385: 117-128Crossref PubMed Scopus (134) Google Scholar). Ischemia is associated with a decline in the EPR signal due to the Rieske ISC protein associated with respiratory complex III (32.Lesnefsky E.J. Gudz T.I. Migita C.T. Ikeda-Saito M. Hassan M.O. Turkaly P.J. Hoppel C.L. Ischemic injury to mitochondrial electron transport in the aging heart: damage to the iron-sulfur protein subunit of electron transport complex III.Arch. Biochem. Biophys. 2001; 385: 117-128Crossref PubMed Scopus (134) Google Scholar). Iron-related proteins in mammals are primarily regulated by the IRP1/IRP2 system (33.Zhang D.L. Ghosh M.C. Rouault T.A. The physiological functions of iron regulatory proteins in iron homeostasis: an update.Front. Pharmacol. 2014; 5: 124Crossref PubMed Scopus (151) Google Scholar). Under iron-deficient cellular conditions, IRP1/2 bind mRNA transcripts of ferritin and TfR1. Doing so increases TfR1 expression and decrease ferritin levels. IRP2−/− mice accumulate large amounts of iron in the liver (33.Zhang D.L. Ghosh M.C. Rouault T.A. The physiological functions of iron regulatory proteins in iron homeostasis: an update.Front. Pharmacol. 2014; 5: 124Crossref PubMed Scopus (151) Google Scholar, 34.Chakrabarti M. Cockrell A.L. Park J. McCormick S.P. Lindahl L.S. Lindahl P.A. Speciation of iron in mouse liver during development, iron deficiency, IRP2 deletion, and inflammatory hepatitis.Metallomics. 2015; 7: 93-101Crossref PubMed Google Scholar, 35.Galy B. Ferring D. Minana B. Bell O. Janser H.G. Muckenthaler M. Schümann K. Hentze M.W. Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2).Blood. 2005; 106: 2580-2589Crossref PubMed Scopus (184) Google Scholar, 36.Zumbrennen-Bullough K.B. Becker L. Garrett L. Hölter S.M. Calzada-Wack J. Mossbrugger I. Quintanilla-Fend L. Racz I. Rathkolb B. Klopstock T. Wurst W. Zimmer A. Wolf E. Fuchs H. Gailus-Durner V. et al.Abnormal brain iron metabolism in IRP2 deficient mice is associated with mild neurological and behavioral impairments.PLOS ONE. 2014; 9: e98072Crossref PubMed Scopus (40) Google Scholar), whereas IRP2−/− brains contain WT levels of iron and WT MB features (34.Chakrabarti M. Cockrell A.L. Park J. McCormick S.P. Lindahl L.S. Lindahl P.A. Speciation of iron in mouse liver during development, iron deficiency, IRP2 deletion, and inflammatory hepatitis.Metallomics. 2015; 7: 93-101Crossref PubMed Google Scholar). MB spectroscopy is the most powerful spectroscopic tool for probing the iron content of biological materials, but it has not been applied extensively to vertebrate animals (37.Chakrabarti M. Lindahl P.A. The Utility of Mössbauer Spectroscopy in Eukaryotic Cell Biology and Animal Physiology.in: Rouault T.A. Iron-sulfur Clusters. Walter de Gruyter Publisher, Berlin Germany2014: 49-75Crossref Scopus (7) Google Scholar). MB is relatively insensitive and can only detect 57Fe, which accounts for just 2% of naturally occurring iron. As a result, spectra of unenriched mammalian organs are noisy, even when iron overloaded. Enriching mammals in 57Fe is inconvenient and costly. Nevertheless, we enriched mice with 57Fe for this study. In earlier studies, we used MB spectroscopy to characterize the iron content of brain and liver (34.Chakrabarti M. Cockrell A.L. Park J. McCormick S.P. Lindahl L.S. Lindahl P.A. Speciation of iron in mouse liver during development, iron deficiency, IRP2 deletion, and inflammatory hepatitis.Metallomics. 2015; 7: 93-101Crossref PubMed Google Scholar, 38.Holmes-Hampton G.P. Chakrabarti M. Cockrell A.L. McCormick S.P. Abbott L.C. Lindahl L.S. Lindahl P.A. Changing iron content of the mouse brain during development.Metallomics. 2012; 4: 761-770Crossref PubMed Scopus (26) Google Scholar, 39.Chakrabarti M. Barlas M.N. McCormick S.P. Lindahl L.S. Lindahl P.A. Kinetic of iron import into developing mouse organs determined by a pup-swapping method.J. Biol. Chem. 2015; 290: 520-528Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). Here we use MB to probe the iron content of healthy mouse hearts during development. We also investigate hearts from HFE−/− mice with hemochromatosis, hearts from IRP2−/− mice, and hearts from an iron-deficient mouse and her offspring. We wanted to characterize the iron content of healthy mammalian hearts at different developmental stages, and used MB spectroscopy as our primary tool. We enriched mice with 57Fe to improve spectral quality. Analyses were augmented by EPR spectroscopy and ICP-MS analysis. Mice were euthanized at different ages and immediately imported into a refrigerated anaerobic glove box where blood was flushed extensively with Ringer's buffer. Hearts and other organs were removed by dissection, and frozen in MB cups for later analysis. Low-field MB spectra were collected on whole intact hearts from elderly (Fig. 1), young (Fig. 2), and adult (Fig. 3) mice. For each group, multiple spectra are shown to help distinguish sample-to-sample variations from age-dependent changes. Distinguishing this is a challenge for studies like this in which only small numbers of animals can be investigated. After collecting spectra, samples were analyzed for metal concentrations. These results, and the MB parameters used in simulations are compiled in Table 1. EPR spectra were collected (Fig. 4) on different heart samples that had been homogenized and packed into EPR tubes by centrifugation.FIGURE 2Mössbauer spectra (5 K) of hearts from young mice. A, C00; B, C01; C, C02a; D, C02b; E, C03; F, C03D; G, C04a; H, C04b.View Large Image Figure ViewerDownload Hi-res image Download (PPT)FIGURE 3Mössbauer spectra (5 K) of hearts from adult mice. A, C06; B, I08; C, C16; D, C24; E, C28; F, C28D.View Large Image Figure ViewerDownload Hi-res image Download (PPT)TABLE 1Metal concentrations in 57Fe-enriched mouse hearts (and livers), and associated Mössbauer parametersSampleMass of heart[57Fe][Fetot][Cu][Mn][Zn]Central doubletFerritin sextetBlood doubletmg%; μm%; μm%; μmC00 (1 day)65 (1)240 ± 3300 ± 810 ± 11.6 ± 0.231 ± 720; 6020; 6060; 180C01100350 ± 7470 ± 1033 ± 14.9 ± 0.143 ± 138; 18017; 8045; 210C02a180 (1)240 ± 9290 ± 1012 ± 0.42.3 ± 0.126 ± 153; 15000; 0047; 140C02b59 (2)170 ± 3240 ± 919 ± 23.3 ± 0.126 ± 146; 11013; 3041; 100C03NDaND, not determined.NDNDNDNDND50; ND0; ND50; NDC04a98 (4)600 ± 8710 ± 929 ± 0.38.9 ± 0.246 ± 140; 28010; 7050; 360C04b61 (2)570 ± 10610 ± 1048 ± 111 ± 0.245 ± 144; 27012; 7044; 270C06140 (1)620 ± 1670 ± 1042 ± 18.1 ± 0.143 ± 136; 24017; 11047; 320C12150 (3)63 ± 1610 ± 1038 ± 15.8 ± 0.137 ± 131; 19032; 19037; 230C16NDNDNDNDNDND33; ND28; ND39; NDC24240 (2)950 ± 81050 ± 845 ± 17.7 ± 0.147 ± 130; 32028; 29042; 440C28140 (2)740 ± 10780 ± 1036 ± 0.45.8 ± 0.134 ± 128; 22036; 28036; 280C52250 (2)700 ± 101100 ± 2039 ± 18.1 ± 0.148 ± 122; 24048; 53030; 330C60130 (1)650 ± 30960 ± 4040 ± 103.4 ± 0.134 ± 116; 15041; 39043; 420C03D (pups)94 (4)260 ± 10310 ± 2040 ± 224 ± 156 ± 25" @default.
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• W2587806613 date "2017-03-01" @default.
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• W2587806613 title "Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels" @default.
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• W2587806613 cites W1965051516 @default.
• W2587806613 cites W1966164221 @default.
• W2587806613 cites W1970096539 @default.
• W2587806613 cites W1972610941 @default.
• W2587806613 cites W1975933947 @default.
• W2587806613 cites W1980018929 @default.
• W2587806613 cites W1981667735 @default.
• W2587806613 cites W1990104589 @default.
• W2587806613 cites W1999236279 @default.
• W2587806613 cites W2000146378 @default.
• W2587806613 cites W2004724037 @default.
• W2587806613 cites W2006047974 @default.
• W2587806613 cites W2022751993 @default.
• W2587806613 cites W2023209642 @default.
• W2587806613 cites W2023926316 @default.
• W2587806613 cites W2025897113 @default.
• W2587806613 cites W2045213984 @default.
• W2587806613 cites W2045949768 @default.
• W2587806613 cites W2049820672 @default.
• W2587806613 cites W2055915264 @default.
• W2587806613 cites W2063560713 @default.
• W2587806613 cites W2068775271 @default.
• W2587806613 cites W2074154058 @default.
• W2587806613 cites W2081768689 @default.
• W2587806613 cites W2086942063 @default.
• W2587806613 cites W2088751122 @default.
• W2587806613 cites W2094745090 @default.
• W2587806613 cites W2105156047 @default.
• W2587806613 cites W2108147335 @default.
• W2587806613 cites W2123393106 @default.
• W2587806613 cites W2127556498 @default.
• W2587806613 cites W2134435694 @default.
• W2587806613 cites W2135140210 @default.
• W2587806613 cites W2142097485 @default.
• W2587806613 cites W2149278525 @default.
• W2587806613 cites W2158892672 @default.
• W2587806613 cites W2167584462 @default.
• W2587806613 cites W2346243518 @default.
• W2587806613 cites W2498215202 @default.
• W2587806613 cites W77619586 @default.
• W2587806613 cites W2073476828 @default.
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