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 Stehling, O.
Right arrow Articles by Lill, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stehling, O.
Right arrow Articles by Lill, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2008, p. 5517-5528, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.00545-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Nbp35 Is Essential for both Cytosolic Iron-Sulfur Protein Assembly and Iron Homeostasis{triangledown}

Oliver Stehling,1 Daili J. A. Netz,1 Brigitte Niggemeyer,1 Ralf Rösser,1 Richard S. Eisenstein,2 Helene Puccio,3 Antonio J. Pierik,1 and Roland Lill1*

Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Robert-Koch-Str. 6, 35033 Marburg, Germany,1 Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, Wisconsin 53706,2 Department of Neurobiology and Genetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U596, CNRS/ULP UMR 7104, 1 Rue Laurent Fries, BP 10142, Illkirch F-67400, France3

Received 4 April 2008/ Returned for modification 2 May 2008/ Accepted 16 June 2008

The maturation of cytosolic iron-sulfur (Fe/S) proteins in mammalian cells requires components of the mitochondrial iron-sulfur cluster assembly and export machineries. Little is known about the cytosolic components that may facilitate the assembly process. Here, we identified the cytosolic soluble P-loop NTPase termed huNbp35 (also known as Nubp1) as an Fe/S protein, and we defined its role in the maturation of Fe/S proteins in HeLa cells. Depletion of huNbp35 by RNA interference decreased cell growth considerably, indicating its essential function. The deficiency in huNbp35 was associated with an impaired maturation of the cytosolic Fe/S proteins glutamine phosphoribosylpyrophosphate amidotransferase and iron regulatory protein 1 (IRP1), while mitochondrial Fe/S proteins remained intact. Consequently, huNbp35 is specifically involved in the formation of extramitochondrial Fe/S proteins. The impaired maturation of IRP1 upon huNbp35 depletion had profound consequences for cellular iron metabolism, leading to decreased cellular H-ferritin, increased transferrin receptor levels, and higher transferrin uptake. These properties clearly distinguished huNbp35 from its yeast counterpart Nbp35, which is essential for cytosolic-nuclear Fe/S protein assembly but plays no role in iron regulation. huNbp35 formed a complex with its close homologue huCfd1 (also known as Nubp2) in vivo, suggesting the existence of a heteromeric P-loop NTPase complex that is required for both cytosolic Fe/S protein assembly and cellular iron homeostasis.

* Corresponding author. Mailing address: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Robert-Koch-Str. 6, 35033 Marburg, Germany. Phone: 49-6421-286 6449. Fax: 49-6421-286 6414. E-mail: lill{at}staff.uni-marburg.de

{triangledown} Published ahead of print on 23 June 2008.

Molecular and Cellular Biology, September 2008, p. 5517-5528, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.00545-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Boyd, J. M., Drevland, R. M., Downs, D. M., Graham, D. E. (2009). Archaeal ApbC/Nbp35 Homologs Function as Iron-Sulfur Cluster Carrier Proteins. J. Bacteriol. 191: 1490-1497 [Abstract] [Full Text]  
  • Bych, K., Netz, D. J. A., Vigani, G., Bill, E., Lill, R., Pierik, A. J., Balk, J. (2008). The Essential Cytosolic Iron-Sulfur Protein Nbp35 Acts without Cfd1 Partner in the Green Lineage. J. Biol. Chem. 283: 35797-35804 [Abstract] [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»