Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jun;161(5):726-737.
doi: 10.1111/bjh.12316. Epub 2013 Apr 10.

Effects of mitochondrial ferritin overexpression in normal and sideroblastic erythroid progenitors

Rosangela Invernizzi  1 , Erica Travaglino  2 , Matteo G Della Porta  2 , Anna Gallì  2 , Luca Malcovati  2 , Vittorio Rosti  3 , Gaetano Bergamaschi  1 , Benedetta G Erba  4 , Francesca Bellistri  1 , Raffaella Bastia  1 , Paolo Santambrogio  4 , Sonia Levi  4   5 , Mario Cazzola  2
Affiliations

Effects of mitochondrial ferritin overexpression in normal and sideroblastic erythroid progenitors

Rosangela Invernizzi et al. Br J Haematol. 2013 Jun.

Abstract

In myelodysplastic syndromes with ring sideroblasts (MDS-RS), the iron deposited in the mitochondria of RS is present in the form of mitochondrial ferritin (FTMT), but it is unknown whether FTMT overexpression is the cause or the result of mitochondrial iron deposition. Lentivirus FTMT-transduced CD34(+) bone marrow cells from seven healthy donors and CD34(+) cells from 24 patients with MDS-RS were cultured according to a procedure that allowed the expansion of high numbers of erythroid progenitors. These cells were used to investigate the possible influence of experimentally-induced FTMT overexpression on normal erythropoiesis and the functional effects of FTMT in sideroblastic erythropoiesis. In MDS-RS progenitors, FTMT overexpression was associated with reduced cytosolic ferritin levels, increased surface transferrin receptor expression and reduced cell proliferation; FTMT effects were independent of SF3B1 mutation status. Similarly, FTMT overexpressing normal erythroid progenitors were characterized by reduced cytosolic ferritin content and increased CD71 expression, and also by higher apoptotic rate in comparison with the FTMT- controls. Significantly lower levels of STAT5 phosphorylation following erythropoietin stimulation were found in both sideroblastic and normal FTMT(+) erythroid cells compared to the FTMT- cells. In conclusion, experimental overexpression of FTMT may modify mitochondrial iron availability and lead to ineffective erythropoiesis.

PubMed Disclaimer

References

    1. Arosio, P. & Levi, S. (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochimica et Biophysica Acta, 1800, 783-792.
    1. Bartnikas, T.B., Campagna, D.R., Antiochos, B., Mulhem, H., Pondarrè, C. & Fleming, M.D. (2010) Characterization of mitochondrial ferritin-deficient mice. American Journal of Hematology, 85, 958-960.
    1. Boultwood, J., Pellagatti, A., Nikpour, M., Pushkaran, B., Fidler, C., Cattan, H., Littlewood, T.J., Malcovati, L., Della Porta, M.G., Jädersten, M., Killick, S., Giagounidis, A., Bowen, D., Hellström-Lindberg, E., Cazzola, M. & Wainscoat, J.S. (2008) The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. PLoS ONE, 3, e1970.
    1. Brunning, R.D., Orazi, A., Germing, U., Le Beau, M.M., Porwit, A., Baumann, I., Vardiman, J.W. & Hellstrom-Lindberg, E. (2008) Myelodysplastic syndromes/neoplasms, overview. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedn (eds by S.H. Swerdlow, E. Campo, N.L. Harris, E.S. Jaffe, S.A. Pileri, H. Stein, J. Thiele, J.W. Vardiman), pp. 88-93. IARC Press, Lyon, France.
    1. Camaschella, C. (2009) Hereditary sideroblastic anemias: pathophysiology, diagnosis, and treatment. Seminars in Hematology, 46, 371-377.

Publication types

MeSH terms

LinkOut - more resources