Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels

• Published in: The Journal of biological chemistry 2017-03, Vol.292 (13), p.5546-5554
• Main Authors: Wofford, Joshua D., Chakrabarti, Mrinmoy, Lindahl, Paul A.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Brain Chemistry; cardiac metabolism; electron paramagnetic resonance (EPR); Electron Spin Resonance Spectroscopy; Ferritins - analysis; Heart; Humans; iron; Iron - analysis; Iron - metabolism; Liver - chemistry; Mice; mitochondria; Mitochondria - chemistry; Molecular Biophysics; Mossbauer spectroscopy; Myocardium - chemistry; Myocardium - metabolism; Specimen Handling - standards; Spectroscopy, Mossbauer - methods
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M117.777201

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.