Mitochondrial Ferritin: A New Player in Iron Metabolism

Drysdale, James W.; Arosio, Paolo; Invernizzi, Rosangela; Cazzola, Mario; Volz, Armin; Corsi, Barbara; Biasiotto, Giorgio; Levi, Sonia

doi:10.1006/bcmd.2002.0577

Cited by 164 publications

(140 citation statements)

References 20 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…Transfection of human cells with human mitochondrial ferritin resulted in cytosolic iron depletion, cytosolic ferritin inhibition, and up-regulation of the transferrin receptor (7)(8)(9). Because Drosophila has no recognizable transferrin receptor, we could not use transferrin receptor expression as an indicator of iron status, and instead, we analyzed the levels of Fer1HCH and Fer2LCH in flies that overexpress Fer3HCH.…”

Section: Fer3hch Overexpression In Vivo Does Not Affect Levels Of Fermentioning

confidence: 99%

“…Mammalian mitochondrial ferritin mRNA does not contain an iron-regulatory element and is expressed in testes, islets of Langerhans and neurons, and at low levels in multiple other tissues (6). Elevated levels of mitochondrial ferritin have been shown to cause cytosolic iron depletion and up-regulation of the transferrin receptor in transfected cell lines (7)(8)(9). Recently, ferritin also was found in plant mitochondria (10).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of mitochondrial ferritin in Drosophila

Missirlis

Holmberg

Georgieva

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

110

111

View full text Add to dashboard Cite

Mitochondrial function depends on iron-containing enzymes and proteins, whose maturation requires available iron for biosynthesis of iron-sulfur clusters and heme. Little is known about how mitochondrial iron homeostasis is maintained, although the recent discovery of a mitochondrial ferritin in mammals and plants has uncovered a potential key player in the process. Here, we show that Drosophila melanogaster expresses mitochondrial ferritin from an intron-containing gene. It has high similarity to the mouse and human mitochondrial ferritin sequences and, as in mammals, is expressed mainly in testis. This ferritin contains a putative mitochondrial targeting sequence and an epitope-tagged version localizes to mitochondria in transfected cells. Overexpression of mitochondrial ferritin fails to alter both total-body iron levels and iron that is bound to secretory ferritins. However, the viability of iron-deficient flies is compromised by overexpression of mitochondrial ferritin, suggesting that it may sequester iron at the expense of other important cellular functions. The conservation of mitochondrial ferritin in an insect species underscores the importance of this iron-storage molecule.iron ͉ metabolism ͉ mitochondria ͉ paraquat ͉ testis

show abstract

Section: Fer3hch Overexpression In Vivo Does Not Affect Levels Of Fermentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of mitochondrial ferritin in Drosophila

Missirlis

Holmberg

Georgieva

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

110

111

View full text Add to dashboard Cite

show abstract

“…1,2 The human protein is encoded by a nuclear intronless gene that is transcribed into a mRNA similar to H-and L-ferritin mRNA, but it lacks the typical consensus iron-responsive element (IRE) sequence for iron-dependent regulation. 3 FtMt has a three-dimensional structure 4 and biochemical properties analogous to those of human H-ferritin. FtMt rapidly incorporates and oxidizes iron in vitro 5 and its expression strongly affects cellular iron homeostasis as, revealed by several studies of cellular and animal models.…”

Section: Introductionmentioning

confidence: 99%

Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation

Santambrogio¹,

Erba²,

Campanella³

et al. 2011

Haematologica

View full text Add to dashboard Cite

Mitochondrial ferritin is a nuclear encoded iron-storage protein localized in mitochondria. It has anti-oxidant properties related to its ferroxidase activity, and it is able to sequester iron avidly into the organelle. The protein has a tissue-specific pattern of expression and is also highly expressed in sideroblasts of patients affected by hereditary sideroblastic anemia and by refractory anemia with ringed sideroblasts. The present study examined whether mitochondrial ferritin has a role in the pathogenesis of these diseases. Design and MethodsWe analyzed the effect of mitochondrial ferritin over-expression on the JAK2/STAT5 pathway, on iron metabolism and on heme synthesis in erythroleukemic cell lines. Furthermore its effect on apoptosis was evaluated on human erythroid progenitors. Results Data revealed that a high level of mitochondrial ferritin reduced reactive oxygen species andStat5 phosphorylation while promoting mitochondrial iron loading and cytosolic iron starvation. The decline of Stat5 phosphorylation induced a decrease of the level of anti-apoptotic BclxL transcript compared to that in control cells; however, transferrin receptor 1 transcript increased due to the activation of the iron responsive element/iron regulatory protein machinery. Also, high expression of mitochondrial ferritin increased apoptosis, limited heme synthesis and promoted the formation of Perls-positive granules, identified by electron microscopy as iron granules in mitochondria. ConclusionsOur results provide evidence suggesting that Stat5-dependent transcriptional regulation is displaced by strong cytosolic iron starvation status induced by mitochondrial ferritin. The protein interferes with JAK2/STAT5 pathways and with the mechanism of mitochondrial iron accumulation.Key words: mitochondrial ferritin, iron acculumation, hereditary sideroblastic anemia, refractory anemia with ringed sideblasts, ROS, iron starvation, JAK2/STA5. 2011;96(10):1424-1432 doi:10.3324/haematol.2011 This is an open-access paper. Citation: Santambrogio P, Erba BG, Campanella A, Cozzi A, Causarano V, Cremonesi L, Gallì A, Della Porta MG, Invernizzi R, and Levi S. Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation. Haematologica Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation

show abstract

“…Mitochondrial ferritin represents another iron -sequestering protein localizing to mitochondria [92]. Overexpression of mitochondrial ferritin leads to iron sequestration within mitochondria, decrease in cytosolic ferritin and an increase in TFR1 expression [92].…”

Section: Storage Of Intracellular Ironmentioning

confidence: 99%

“…Overexpression of mitochondrial ferritin leads to iron sequestration within mitochondria, decrease in cytosolic ferritin and an increase in TFR1 expression [92]. Another important iron storage complex is hemosiderin (see Figure 1.2).…”

Section: Storage Of Intracellular Ironmentioning

confidence: 99%