Mitochondrial Iron Metabolism and Sideroblastic Anemia

Sheftel, Alex D.; Richardson, Des R.; Prchal, Josef T.; Ponka, Prem

doi:10.1159/000243796

Cited by 40 publications

(33 citation statements)

References 126 publications

(96 reference statements)

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“…Additional cytosolic protein chaperones are believed to transport iron to mitochondria in a chelator-impermeable, endosome-independent manner (402). Depending on the cell lineage, however, the specific transport mechanism may vary (396). A third hypothesis proposes the ''kiss and run'' mechanism of iron delivery to the mitochondria, especially in developing reticulocytes (397).…”

Section: A Iron Uptake and Utilization In The Mitochondriamentioning

confidence: 99%

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Singh

Haldar

Tripathi

et al. 2014

Antioxidants & Redox Signaling

176

165

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Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mismetabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324Signal. 20, -1363

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Section: A Iron Uptake and Utilization In The Mitochondriamentioning

confidence: 99%

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Singh

Haldar

Tripathi

et al. 2014

Antioxidants & Redox Signaling

176

165

View full text Add to dashboard Cite

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“…(21) Sideroblastic anaemia is heterogeneous and characterised by excess iron accumulation in the mitochondria of erythroblasts. (11,26) The morphological hallmark of sideroblastic anaemia is the ring sideroblast, a pathological erythroid precursor containing an excessive amount of non-heme iron deposits in the mitochondria with perinuclear distribution, generating a ring appearance. (26) Sideroblastic anaemia may be hereditary or acquired.…”

Section: Syndromicmentioning

confidence: 99%

“…(11,26) The morphological hallmark of sideroblastic anaemia is the ring sideroblast, a pathological erythroid precursor containing an excessive amount of non-heme iron deposits in the mitochondria with perinuclear distribution, generating a ring appearance. (26) Sideroblastic anaemia may be hereditary or acquired. Hereditary sideroblastic anaemia may be caused by mutations in nDNA-located genes such as ALAS2, ABCB7, GRLX5, SLC25A38, SF3B1, JAK2, TET2, MPLW515 and YARS2, or by large mtDNA deletions.…”

Section: Syndromicmentioning

confidence: 99%

“…Hereditary sideroblastic anaemia may be caused by mutations in nDNA-located genes such as ALAS2, ABCB7, GRLX5, SLC25A38, SF3B1, JAK2, TET2, MPLW515 and YARS2, or by large mtDNA deletions. (26) Acquired sideroblastic anaemia can be primary (refractory anaemia with ring sideroblasts [RARS]), representing a subtype of myelodysplastic syndrome, or secondary (due to drugs, toxins, copper deficiency or malignancy). Ring sideroblasts may develop as a result of defective heme synthesis in erythroblasts (as in XLSA), a defect in the Fe-S cluster assembly, release of Fe-S protein precursor from the mitochondria (as in XLSA-A) or defective intracellular iron metabolism in erythroid cells (as in RARS).…”

Section: Syndromicmentioning

confidence: 99%

“…Ring sideroblasts may develop as a result of defective heme synthesis in erythroblasts (as in XLSA), a defect in the Fe-S cluster assembly, release of Fe-S protein precursor from the mitochondria (as in XLSA-A) or defective intracellular iron metabolism in erythroid cells (as in RARS). (11,26) Thrombopenia has been occasionally reported in patients with MIDs. Although thrombopenia is more frequently seen in Pearson syndrome, (6) it can also occur in Kearns-Sayre syndrome.…”

Section: Syndromicmentioning

confidence: 99%

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Mitochondrial Iron Metabolism and Sideroblastic Anemia

Cited by 40 publications

References 126 publications

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Haematological abnormalities in mitochondrial disorders

The cytologic criteria of malignancy

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