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

It has been reported that the mitochondrial cytochromes and citrate cycle enzymes occur in constant proportions to each other and increase or decrease roughly in parallel in response to various stimuli. The purpose of this study was to determine whether this proportionality is an obligatory consequence of the way in which mitochondria are assembled. Severe iron deficiency was used to bring about decreases of the iron-containing constituents of the mitochondrial respiratory chain in skeletal muscle. Cytochrome c concentration and cytochrome oxidase activity were decreased approximately 50%, while succinate dehydrogenase and NADH dehydrogenase activities were decreased by 78% in iron-deficient muscle. On electron microscopic examination, mitochondria in iron-deficient muscles had relatively sparse numbers of cristae. The iron deficiency had little or no effect on the levels of a range of mitochondrial matrix enzymes, including citrate synthase, isocitrate dehydrogenase, fumarase, aspartate aminotransferase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and acetoacetyl-CoA thiolase. These results show that the usual constant proportions between the constituents of the mitochondrial respiratory chain and matrix enzymes are not obligatory; they provide evidence that mitochondrial matrix enzymes and respiratory chain constituents can be incorporated into mitochondria independently and that the ratios between them can vary within wide limits.
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PMID:Perturbation of mitochondrial composition in muscle by iron deficiency. Implications regarding regulation of mitochondrial assembly. 302 53

Submitochondrial particles prepared from liver and skeletal muscle of control and iron-deficient rats were examined for cytochrome content and for both energy-independent and energy-conserving functions. Liver submitochondrial particles appear quite resistant to iron deficiency with cytochrome content and electron-transferring or energy-conserving functions maintained at a level of 85% or better of normal. Iron-deficient skeletal muscle submitochondrial particles, in contrast, have decreased cytochrome content and only 15-20% of the normal capacity for oxidation through either complex I (NADH dehydrogenase) or complex II (succinate dehydrogenase). Energy-linked reactions which involve substrate oxidation/reduction (succinate----NAD+ reversed electron flow and succinate-driven energy-dependent transhydrogenation) are likewise markedly decreased, while ATP-driven energy-dependent transhydrogenation and mitochondrial ATPase are normal. Our data support the concept that iron deficiency leads to decreased electron-carrying capacity of iron-containing mitochondrial enzymes, with skeletal muscle being much more susceptible than liver, but that the mitochondria are otherwise normal with regard to energy conservation.
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PMID:Effect of iron deficiency on energy conservation in rat liver and skeletal muscle submitochondrial particles. 405 63

Iron may affect both respiratory O2 transport and mitochondrial electron transport in the performance of muscle work. This study was designed to elucidate the molecular defect of iron-deficient work performance by identifying heretofore unmeasurable mitochondrial enzymes that are diminished by iron deficiency and may be restored by iron repletion. Female rats were made iron-deficient by dietary control and were repleted by oral iron. Iron deficiency reduced physical work capacity (treadmill running time), haemoglobin (Hb), and mitochondrial iron-sulphur (Fe-S) centres in heart and skeletal muscles; mitochondrial number was unaffected. Oral iron supplementation restored work capacity and Hb within 4 d to normal or near-normal levels, but in general Fe-S centres of mitochondria due to NADH dehydrogenase remained at iron-deficient levels. Subnormal concentrations of mitochondrial iron-dependent NADH dehydrogenase in muscle are not by themselves rate-limiting in work performance.
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PMID:Mitochondrial NADH dehydrogenase in iron-deficient and iron-repleted rat muscle: an EPR and work performance study. 629 76

The effects of iron deficiency on the NADH- and succinate-oxidizing complexes of rat skeletal muscle mitochondria have been investigated. Both systems were similarly affected: activities were about 30% of normal in dehydrogenase, ubiquinone reductase, and oxidase assays, and similar reductions in the concentration of their respective flavin prosthetic groups were also evident in the iron-deficient membranes. Thus, the turnover numbers of the two enzymes were unchanged in iron deficiency. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed similarly reduced levels of those peptide components of Complexes I and II that could be unequivocally distinguished. Soluble beef heart succinate dehydrogenase added to alkaline-treated rat skeletal muscle mitochondrial membranes attached to binding sites exposed by the treatment, forming a hybrid complex indistinguishable from the original skeletal muscle complex, with restoration of succinoxidase and succinate-ubiquinone reductase activities to the levels observed in the original rat membranes. Iron-deficient particles behaved like the normal in these tests. No unfilled binding sites for the enzyme could be detected prior to alkaline treatment. The data are interpreted as indicating that the lower activities of these two respiratory complexes in iron deficiency are due to lower content of the enzymes rather than to the presence of impaired enzymes in the membrane, that only fully competent complexes are present in these membranes, and that iron-deficient complexes are either not assembled or are lost after assembly.
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PMID:Effect of iron deficiency on succinate- and NADH-ubiquinone oxidoreductases in skeletal muscle mitochondria. 643 78

Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins that are central regulators of mammalian iron homeostasis. We investigated the time-dependent effect of dietary iron deficiency on liver IRP activity in relation to the abundance of ferritin and the iron-sulfur protein mitochondrial aconitase (m-acon), which are targets of IRP action. Rats were fed a diet containing 2 or 34 mg iron/kg diet for 1-28 d. Liver IRP activity increased rapidly in rats fed the iron-deficient diet with IRP1 stimulated by d 1 and IRP2 by d 2. The maximal activation of IRP2 was five-fold (d 7) and three-fold (d 4) for IRP1. By d 4, liver ferritin subunits were undetectable and m-acon abundance eventually fell by 50% (P < 0.05) in iron-deficient rats. m-Acon abundance declined most rapidly from d 1 to 11 and in a manner that was suggestive of a cause and effect type of relationship between IRP activity and m-acon abundance. In liver, iron deficiency did not decrease the activity of cytosolic aconitase, catalase or complex I of the electron transport chain nor was there an effect on the maximal rate of mitochondrial oxygen consumption with the use of malate and pyruvate as substrates. Thus, the decline in m-acon abundance in iron deficiency is not reflective of a global decrease in liver iron-sulfur proteins nor does it appear to limit ATP production. Our results suggest a novel role for m-acon in cellular iron metabolism. We conclude that, in liver, iron deficiency preferentially affects the activities of IRPs and the targets of IRP action.
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PMID:Dietary iron intake rapidly influences iron regulatory proteins, ferritin subunits and mitochondrial aconitase in rat liver. 948 59

Iron deficiency affects the function of the respiratory chain, primarily at the complex I and complex II levels. Because plant mitochondria possess alternative NAD(P)H dehydrogenases located in the inner membrane, oxidizing NAD(P)H from both cytosol and matrix, we investigated these activities in mitochondria of Fe-deficient roots. External and internal NAD(P)H dehydrogenase activity increased in Fe-deficient mitochondria. Accordingly, NDB1 protein strongly accumulated, while NDA1 did not show differences in Fe-deficient roots. The data presented support, for the first time, the hypothesis that Fe deficiency induces the alternative NAD(P)H dehydrogenases, bypassing the impaired complex I.
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PMID:Effect of Fe deficiency on mitochondrial alternative NAD(P)H dehydrogenases in cucumber roots. 2011 82

Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that inhibition of complex I and iron accumulation are hallmarks of idiopathic Parkinson's disease, the findings reported here may have relevance for understanding the pathophysiology of this disease.
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PMID:Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity. 2157 Sep 52

Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp display cardiac dysfunction with iron deficiency, demonstrating that TTP is necessary for maintaining cardiac function in the setting of low cellular iron. Altogether, our results describe a pathway that is activated in iron deficiency to regulate mitochondrial function to match the availability of Fe/S clusters.
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PMID:mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function. 2991 44