This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Paradkar, P. N.
Right arrow Articles by Kaplan, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paradkar, P. N.
Right arrow Articles by Kaplan, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2009, p. 1007-1016, Vol. 29, No. 4
0270-7306/09/$08.00+0     doi:10.1128/MCB.01685-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Regulation of Mitochondrial Iron Import through Differential Turnover of Mitoferrin 1 and Mitoferrin 2 {triangledown}

Prasad N. Paradkar,1 Kimberley B. Zumbrennen,2 Barry H. Paw,3 Diane M. Ward,1 and Jerry Kaplan1*

Department of Pathology, University of Utah School of Medicine,1 Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84132,2 Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 021153

Received 30 October 2008/ Accepted 2 December 2008

Mitoferrin 1 and mitoferrin 2 are homologous members of the mitochondrial solute carrier family. Mitoferrin 1 is required for mitochondrial iron delivery in developing erythrocytes. Here we show that mitoferrin 1 and mitoferrin 2 contribute to mitochondrial iron delivery in a variety of cells. Reductions in mitoferrin 1 and/or mitoferrin 2 levels by RNA interference result in decreased mitochondrial iron accumulation, heme synthesis, and iron-sulfur cluster synthesis. The ectopic expression of mitoferrin 1 in nonerythroid cells silenced for mitoferrin 2 or the expression of mitoferrin 2 in cells silenced for mitoferrin 1 restored heme synthesis to "baseline" levels. The ectopic expression of mitoferrin 2, however, did not support hemoglobinization in erythroid cells deficient in mitoferrin 1. Mitoferrin 2 could not restore heme synthesis in developing erythroid cells because of an inability of the protein to accumulate in mitochondria. The half-life of mitoferrin 1 was increased in developing erythroid cells, while the half-life of mitoferrin 2 did not change. These results suggest that mitochondrial iron accumulation is tightly regulated and that controlling mitoferrin levels within the mitochondrial membrane provides a mechanism to regulate mitochondrial iron levels.

* Corresponding author. Mailing address: Department of Pathology, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132. Phone: (801) 581-7427. Fax: (801) 585-6364. E-mail: jerry.kaplan{at}path.utah.edu

{triangledown} Published ahead of print on 15 December 2008.

Molecular and Cellular Biology, February 2009, p. 1007-1016, Vol. 29, No. 4
0270-7306/09/$08.00+0     doi:10.1128/MCB.01685-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chen, W., Paradkar, P. N., Li, L., Pierce, E. L., Langer, N. B., Takahashi-Makise, N., Hyde, B. B., Shirihai, O. S., Ward, D. M., Kaplan, J., Paw, B. H. (2009). From the Cover: Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc. Natl. Acad. Sci. USA 106: 16263-16268 [Abstract] [Full Text]  
  • Andrews, N. C. (2009). ABCs of erythroid mitochondrial iron uptake. Proc. Natl. Acad. Sci. USA 106: 16012-16013 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»