CGM - Department Cellular and Integrative Biology
Biogenesis and function of mitochondrial respiratory complexes
Team leader: G. Dujardin
Last update: 31-Aug-2010
Mitochondrial network in yeast cells
Our team
Geneviève Dujardin, Staff Scientist, CNRS
Bernard Guiard, Staff Scientist, CNRS
Brigitte Meunier, Staff Scientist, CNRS
Sophie Marsy, Technician, CNRS
Cristina Panozzo, Associated Professor, Université Paris-Sud 11
Jelena Ostojic, PhDStudent
Cindy Vallières, Doctoral Student
Address
CNRS
Centre de Génétique Moléculaire
Avenue de la Terrasse - Bât. 26
91198 GIF-SUR-YVETTE Cedex
FRANCE
Phone: 33 (0)1 69 82 31 69
Telecopy: 33 (0)1 69 82 31 60
Research themes
The respiratory chain, formed by five enzymatic complexes embedded in the inner mitochondrial membrane produces most of the ATP in animal cells, which means more than 65 Kg of ATP daily in an adult. The constant need in energy to maintain cellular metabolism is demanding. Dysfunction of the respiratory chain can have severe consequences on the cells. In humans, it is the cause of diverse metabolic disorders and could be involved in the development of neurodegenerative diseases and of cancers.
The complexe III
The biogenesis of the multi-protein respiratory complexes, of double origin, nuclear and mitochondrial, is a complicated process, which requires several auxiliary factors. The subunits of nuclear origin, translated in the cytoplasm, are imported into the mitochondria and precisely assembled with the mitochondrial subunits and the co-factors. In order to investigate the biogenesis and the function of the respiratory complexes, we use the yeast S. cerevisae as a model of higher eukaryotic cells and a range of molecular genetic and biochemical approaches. Our team is currently studying the molecular mechanisms of mitochondrial import, the role of auxiliary factors, called Oxa1, Rmd9 and Bsc1, in the assembly of the respiratory complexes, and the functioning of these complexes, in particular, complex III and the impact of minor modifications of its structure.
Further details about the 3 research themes
Theme "Control of the assembly of respiratory complexes" : G. Dujardin
Theme "Function and dysfunction of respiratory complexes" : B. Meunier
Theme "Import of mitochondrial proteins" : B. Guiard
Representative publications since 2007
Mathieu, L., Bourens, M., Marsy, S., Hlavacek, O., Panozzo, C. and Dujardin, G. (2010) A mutational analysis reveals new functional interactions between domains of the Oxa1 protein in Saccharomyces cerevisiae. Mol Microbiol, 75 (2) 474-88.
Panozzo, C., Bourens, M., Nowacka, A. and Herbert, C.-J. (2010) Mutations in the C-terminus of the conserved NDR kinase, Cbk1p of Saccharomyces cerevisiae, make the protein independent of upstream activators. Mol Genet Genomics, 283 (2) 111-22.
Nouet, C., Truan, G., Mathieu, L. and Dujardin, G. (2009) Functional Analysis of Yeast bcs1 Mutants Highlights the Role of Bcs1p-Specific Amino Acids in the AAA Domain. J Mol Biol, 388 (2) 252-61.
Bourges, I., Mucchielli, M.-H., Herbert, C.-J., Guiard, B., Dujardin, G. and Meunier, B. (2009) Multiple Defects in the Respiratory Chain Lead to the Repression of Genes Encoding Components of the Respiratory Chain and TCA Cycle Enzymes. J Mol Biol, 23 (1) 23-42.
Baker, M. J., Webb, C. T., Stroud, D. A., Palmer, C. S., Frazier, A. E., Guiard, B., Chacinska, A., Gulbis, J. M. and Ryan, M. T. (2009) Structural and functional requirements for activity of the Tim9-Tim10 complex in mitochondrial protein import. Mol Biol Cell, 20 (3) 769-79.
Fisher, N. and Meunier, B. (2008) Molecular basis of resistance to cytochrome bc1 inhibitors. FEMS Yeast Res 8 (2) 183-192.
Wagner, K., Gebert, N., Guiard, B., Brandner, K., Truscott, K.-N., Wiedemann, N., Pfanner, N. and Rehling, P. (2008) The Assembly Pathway of the Mitochondrial Carrier Translocase Involves four Preprotein Translocases. Mol Cell Biol, 28 (13) 4251-60.
Kutik, S., Stojanovski, D., Becker, L., Becker, T., Meinecke, M., Krüger, V., Prinz, C., Meisinger, C., Guiard, B., Wagner, R., Pfanner, N. and Wiedemann, N. (2008) Dissecting membrane insertion of mitochondrial beta-barrel proteins. Cell, 132 (6) 1011-24.
Wenz, T., Covian, R., Hellwig, P., Macmillan, F., Meunier, B., Trumpower, B. and Hunte, C. (2007) Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III. J Biol Chem, 282 (6) 3977-88.
Nouet, C., Bourens, M.,Hlavacek, O., Marsy, S., Lemaire, C., and Dujardin G. (2007) Rmd9p controls the processing/stability of mitochondrial mRNAs and its overexpression compensates for a partial deficiency of Oxa1p in Saccharomyces cerevisiae. Genetics, 175 (3) 1105-15.
van der Laan, M., Meinecke, M., Dudek, J., Hutu, D.-P., Lind, M., Perschil, I., Guiard, B., Wagner, R., Pfanner, N. and Rehling, P. (2007) Motor-free mitochondrial presequence translocase drives membrane integration of preproteins. Nat Cell Biol, 9 (20) 1152-1159.
Thesis
- Nouet, C. (2008) Biogenèse des complexes respiratoires mitochondriaux chez la levure Saccharomyces cerevisiae et les cellules humaines.
Université Versailles Saint-Quentin. Thesis director: G. Dujardin
- Bernard, D. (2006) Biogenèse des cytochromes de type c dans la mitochondrie chez la levure Saccharomyces cerevisiae.
Université Paris Sud 11 Orsay. Thesis director: B. Guiard
- Y. Saint-Georges (2003) Contribution à l’étude de l’assemblage des complexes respiratoires chez S. cerevisiae,
Université Paris Sud 11 - Thesis director: G. Dujardin.
