|
|
Blood, 15 April 2007, Vol. 109, No. 8, pp. 3552-3559.
Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2006-08-041632.
 Previous Article | Next Article 
Submitted August 15, 2006
Accepted November 22, 2006
RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload
Patrizia Cavadini, Giorgio Biasiotto, Maura Poli, Sonia Levi, Rosanna Verardi, Isabella Zanella, Manuela Derosas, Rosaria Ingrassia, Marcella Corrado, and Paolo Arosio*
Dipartimento Materno Infantile e Tecnologie Biomediche, University of Brescia, Brescia, Italy
Unit of Proteomics of Iron Metabolism, Vita e Salute San Raffaele University, Milano, Italy
Section of Immunoematology and Transfusional Medicine, Brescia, Italy
* Corresponding author; email: arosio{at}med.unibs.it.
X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa cells by performing sequential transfections with siRNAs. The phenotype of the ABCB7-deficient cells consisted in a strong reduction in proliferation rate that was not rescued by iron supplementation, by evident signs of iron deficiency, by a large ~6 fold increase of iron accumulation in the mitochondria that was poorly available to mitochondrial ferritin. The cells showed an increase of protoporphyrin IX, a higher sensitivity to H2O2 toxicity and a reduced activity of mitochondrial superoxide dismutase (SOD2), while the activity of mitochondrial enzymes like citrate synthase or succinate dehydrogenase, and ATP content was not decreased. In contrast, aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced. The results support the hypothesis that ABCB7 is involved in the transfer of iron from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In addition, they indicate that anemia in XLSA/A is caused by the accumulation of iron in a form that is not readily usable for heme synthesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. D. Sheftel, O. Stehling, A. J. Pierik, D. J. A. Netz, S. Kerscher, H.-P. Elsasser, I. Wittig, J. Balk, U. Brandt, and R. Lill
Human Ind1, an Iron-Sulfur Cluster Assembly Factor for Respiratory Complex I
Mol. Cell. Biol.,
November 15, 2009;
29(22):
6059 - 6073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Naranuntarat, L. T. Jensen, S. Pazicni, J. E. Penner-Hahn, and V. C. Culotta
The Interaction of Mitochondrial Iron with Manganese Superoxide Dismutase
J. Biol. Chem.,
August 21, 2009;
284(34):
22633 - 22640.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lynch, Y. Fukuda, P. Krishnamurthy, G. Du, and J. D. Schuetz
Cell Survival under Stress Is Enhanced by a Mitochondrial ATP-Binding Cassette Transporter That Regulates Hemoproteins
Cancer Res.,
July 1, 2009;
69(13):
5560 - 5567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Stehling, D. J. A. Netz, B. Niggemeyer, R. Rosser, R. S. Eisenstein, H. Puccio, A. J. Pierik, and R. Lill
Human Nbp35 Is Essential for both Cytosolic Iron-Sulfur Protein Assembly and Iron Homeostasis
Mol. Cell. Biol.,
September 1, 2008;
28(17):
5517 - 5528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Hellstrom-Lindberg and M. Cazzola
The Role of JAK2 Mutations in RARS and Other MDS
Hematology,
January 1, 2008;
2008(1):
52 - 59.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
