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

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 Fe-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 [FeS] clusters and low-spin Fe 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 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. livers were overloaded with ferritin but had low mitochondrial iron levels. 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 Fe 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.

Study of iron complexes in visceral organs and brain from a 57Fe enriched β-thalassaemia mouse model via Mössbauer spectroscopy

“…Ferritin and haemosiderin isolated from iron-overloaded human spleens has also been investigated by MS, at the temperatures of 1.3 and 200K [10]. The brain, liver and hearts of 57 Fe enriched healthy mice were studied by various researchers [11][12][13]. Haemoglobin from residual blood, ferritin, mitochondrial iron, and mononuclear non-haem high-spin (NHHS) Fe(II) and Fe(III) species were identified in brain samples [12].…”

Keeping heart homeostasis in check through the balance of iron metabolism

“…This suspicion is based on the high correlation between DMT1 mRNA and cardiac iron content in these rats. Interestingly, levels of cytosolic iron storage ferritin in the heart also increase with ageing, which would suggest an increased tendency for oxidative damage in ageing hearts …”

“…One of the micronutrients that are needed for proper mitochondrial function is iron. Data suggest that nearly one‐third of cardiomyocyte iron is distributed in mitochondria . In addition, cardiomyocyte mitochondria have 50%‐150% more iron compared to other cells .…”

“…Data suggest that nearly one‐third of cardiomyocyte iron is distributed in mitochondria . In addition, cardiomyocyte mitochondria have 50%‐150% more iron compared to other cells . This level of iron is maintained with constant supply, which should be a subject of tight control, because any reduction in iron supply will affect cellular energetics, while any iron overload will result in mitochondrial damage by ROS .…”

“…This might seem intuitive if one takes into account high iron utilization by the mitochondrial biochemical protein machinery . Furthermore, levels of iron storage in mtFT are low compared to very high iron deposition in cytosolic ferritin . In any case, mtFT emerges as an important protein that is used by cardiomyocytes to control the level of oxidative damage, especially in conditions with MIO.…”