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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron is an essential co-factor for several metabolic processes, including mitochondrial respiration, and mitochondria are the major sites of iron-utilization. Cellular iron homeostasis must be tightly regulated, as intracellular iron deficiency can lead to insufficient energy production, whereas iron overload triggers ROS (reactive oxygen species) formation via the Fenton reaction. So far little is known on how iron imbalances affect mitochondrial function in vivo and the impact of the genotype on that, we studied the effects of dietary iron loading on mitochondrial respiratory capacity in liver by comparing two genetically divergent mouse strains, namely C57BL/6N and FVB mice. Both mouse strains differed in their basal iron levels and their metabolic responses to iron loading as determined by expression of iron trafficking proteins (ferritin was increased in livers of animals receiving high iron diet) as well as tissue iron content (2-fold increase, FVB p = 0.0013; C57BL/6N p = 0.0022). Dietary iron exposure caused a significant impairment of mitochondrial oxidative phosphorylation, especially regarding OXPHOS capacity (FVB p = 0.0006; C57BL/6N p = 0.0087) and S-ETS capacity (FVB p = 0.0281; C57BL/6N p = 0.0159). These effects were more pronounced in C57BL/6N than in FVB mice and were paralleled by an iron mediated induction of oxidative stress in mitochondria. The increased susceptibility of C57BL6/N mice to iron loading may be due to reduced expression of anti-oxidant defense mechanisms and altered iron trafficking upon dietary challenge pointing to a role of genetic modifiers for cellular and mitochondrial iron trafficking. Finally, iron-mediated induction of mitochondrial oxidative stress and reduction of oxidative phosphorylation may underlie fatigue in subjects with iron loading diseases.
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PMID:Dietary iron loading negatively affects liver mitochondrial function. 2902 1

In this study, we aimed to explore how cellular iron status affects embryonic haematopoiesis. For this purpose, we used a model of mouse embryonic stem cell differentiation into embryonic haematopoietic progenitors. We modulated the iron status by adding either the iron chelator Deferoxamine (DFO) for iron deficiency, or ferric ammonium citrate for iron excess, and followed the emergence of developing haematopoietic progenitors. Interestingly, we found that iron deficiency did not block the endothelial to haematopoietic transition, the first step of haematopoiesis. However, it did reduce the proliferation, survival and clonogenic capacity of haematopoietic progenitors. Surprisingly, iron deficiency affected erythro-myeloid progenitors significantly more than the primitive erythroid ones. Erythro-myeloid progenitors expressed less transferrin-receptor on the cell surface and had less labile iron compared to primitive erythroid progenitors, which could reduce their capacity to compete for scarce iron and survive iron deficiency. In conclusion, we show that iron deficiency could disturb haematopoiesis at an early embryonic stage by compromising more severely the survival, proliferation and differentiation of definitive haematopoietic progenitors compared to restricted erythroid progenitors.
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PMID:Iron deficiency disrupts embryonic haematopoiesis but not the endothelial to haematopoietic transition. 3101 68