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 Lazarou, M.
Right arrow Articles by Ryan, M. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lazarou, M.
Right arrow Articles by Ryan, M. T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2007, p. 4228-4237, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.00074-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Analysis of the Assembly Profiles for Mitochondrial- and Nuclear-DNA-Encoded Subunits into Complex I{triangledown}

Michael Lazarou,1 Matthew McKenzie,1 Akira Ohtake,1,2 David R. Thorburn,3 and Michael T. Ryan1*

Department of Biochemistry, La Trobe University, 3086 Melbourne, Australia,1 Department of Pediatrics, Saitama Medical University, Saitama, Japan,2 Murdoch Childrens Research Institute and Genetic Health Services Victoria, Royal Children's Hospital, and Department of Pediatrics, University of Melbourne, Melbourne, Australia3

Received 15 January 2007/ Returned for modification 14 February 2007/ Accepted 5 April 2007

Complex I of the respiratory chain is composed of at least 45 subunits that assemble together at the mitochondrial inner membrane. Defects in human complex I result in energy generation disorders and are also implicated in Parkinson's disease and altered apoptotic signaling. The assembly of this complex is poorly understood and is complicated by its large size and its regulation by two genomes, with seven subunits encoded by mitochondrial DNA (mtDNA) and the remainder encoded by nuclear genes. Here we analyzed the assembly of a number of mtDNA- and nuclear-gene-encoded subunits into complex I. We found that mtDNA-encoded subunits first assemble into intermediate complexes and require significant chase times for their integration into the holoenzyme. In contrast, a set of newly imported nuclear-gene-encoded subunits integrate with preexisting complex I subunits to form intermediates and/or the fully assembly holoenzyme. One of the intermediate complexes represents a subassembly associated with the chaperone B17.2L. By using isolated patient mitochondria, we show that this subassembly is a productive intermediate in complex I assembly since import of the missing subunit restores complex I assembly. Our studies point to a mechanism of complex I biogenesis involving two complementary processes, (i) synthesis of mtDNA-encoded subunits to seed de novo assembly and (ii) exchange of preexisting subunits with newly imported ones to maintain complex I homeostasis. Subunit exchange may also act as an efficient mechanism to prevent the accumulation of oxidatively damaged subunits that would otherwise be detrimental to mitochondrial oxidative phosphorylation and have the potential to cause disease.

* Corresponding author. Mailing address: Department of Biochemistry, La Trobe University, 3086 Melbourne, Australia. Phone: 61-3-94792156. Fax: 61-3-94792467. E-mail: M.Ryan{at}latrobe.edu.au

{triangledown} Published ahead of print on 16 April 2007.

Molecular and Cellular Biology, June 2007, p. 4228-4237, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.00074-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Janssen, R. J.R.J., Distelmaier, F., Smeets, R., Wijnhoven, T., Ostergaard, E., Jaspers, N. G.J., Raams, A., Kemp, S., Rodenburg, R. J.T., Willems, P. H.M.G., van den Heuvel, L. P.W.J., Smeitink, J. A.M., Nijtmans, L. G.J. (2009). Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder. Hum Mol Genet 18: 3365-3374 [Abstract] [Full Text]  
  • Baker, M. J., Webb, C. T., Stroud, D. A., Palmer, C. S., Frazier, A. E., Guiard, B., Chacinska, A., Gulbis, J. M., Ryan, M. T. (2009). Structural and Functional Requirements for Activity of the Tim9-Tim10 Complex in Mitochondrial Protein Import. Mol. Biol. Cell 20: 769-779 [Abstract] [Full Text]  
  • Pello, R., Martin, M. A., Carelli, V., Nijtmans, L. G., Achilli, A., Pala, M., Torroni, A., Gomez-Duran, A., Ruiz-Pesini, E., Martinuzzi, A., Smeitink, J. A., Arenas, J., Ugalde, C. (2008). Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease. Hum Mol Genet 17: 4001-4011 [Abstract] [Full Text]  
  • Dieteren, C. E. J., Willems, P. H. G. M., Vogel, R. O., Swarts, H. G., Fransen, J., Roepman, R., Crienen, G., Smeitink, J. A. M., Nijtmans, L. G. J., Koopman, W. J. H. (2008). Subunits of Mitochondrial Complex I Exist as Part of Matrix- and Membrane-associated Subcomplexes in Living Cells. J. Biol. Chem. 283: 34753-34761 [Abstract] [Full Text]  
  • Pineau, B., Layoune, O., Danon, A., De Paepe, R. (2008). L-Galactono-1,4-lactone Dehydrogenase Is Required for the Accumulation of Plant Respiratory Complex I. J. Biol. Chem. 283: 32500-32505 [Abstract] [Full Text]  
  • McFarland, M. A., Ellis, C. E., Markey, S. P., Nussbaum, R. L. (2008). Proteomics Analysis Identifies Phosphorylation-dependent {alpha}-Synuclein Protein Interactions. Mol. Cell. Proteomics 7: 2123-2137 [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»