CGM - Department Regulation and Compartmentalization of Cellular Functions
Biogenesis and function of mitochondrial respiratory complexes
Team leader: G. Dujardin
Last update: 16-Feb-2012
Mitochondrial network in yeast cells
Our team
Geneviève Dujardin, Staff Scientist, CNRS
Annie Glatigny, Engineer, CNRS
Bernard Guiard, Staff Scientist, CNRS
Brigitte Meunier, Staff Scientist, CNRS
Marie-Hélène Mucchielli-Giorgi, Associated Professor, UPMC
Cristina Panozzo, Associated Professor, Université Paris-Sud 11
Jelena Ostojic, PhD Student
Cindy Vallières, PhD 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 complex 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, as well as the interaction networks involving the different actors of this biogenesis.
Further details about the four research themes
Theme "Biogenesis of mitochondrial respiratory complexes" : G. Dujardin
Theme "Function and dysfunction of respiratory complexes" : B. Meunier
Theme "Import of mitochondrial proteins" : B. Guiard
Theme "In silico modelling of the biogenesis of protein complexes" : M.-H. Mucchielli
Representative publications since 2007
Corvest, V., Murrey, DA., Hirasawa, M., Knaff, DB., Guiard, B., Hamel, PP. (2012) The flavoprotein Cyc2p, a mitochondrial cytochrome c assembly factor is a NAD(P)H-dependent haem réductase. Mol Microbiol, in press.
Trouillard, M., Meunier, B., Rappaport, F. (2011) Questioning the functional relevance of mitochondrial supercomplexes by time-resolved analysis of the respiratory chain. Proc Natl Acad Sci U S A., 108 (45) E1027-34.
Glatigny, A., Mathieu, L., Herbert, CJ., Dujardin, G., Meunier, B., Mucchielli-Giorgi, MH. (2011) An in silico approach combined with in vivo experiments enables the identification of a new protein whose overexpression can compensate for specific respiratory defects in Saccharomyces cerevisiae. BMC Syst Biol, 5 (1) 173.
Gebert, N., ...., Guiard, B., ... van der Laan, M., Pfanner, N., Wiedemann, N. (2011) Dual Function of Sdh3 in the Respiratory Chain and TIM22 Protein Translocase of the Mitochondrial Inner Membrane. Mol Cell, 44 (5) 811-8.
Vallières, C., Trouillard, M., Dujardin, G., Meunier, B. (2011) Studying the deleterious effect of the QoI resistance mutation G143A in the intron-containing cytochrome b gene and the by-pass mechanisms. Appl Environ Microbiol, 77 (6) 2088-93.
Mathieu, L., Marsy, S., Saint-Georges ,Y., Jacq, C., Dujardin, G. (2010) A transcriptome screen in yeast identifies a novel assembly factor for the mitochondrial complex III. Mitochondrion, 77 (6) 2088-93.
Corvest, V., Murrey, DA., Bernard, DG., Knaff, DB., Guiard, B., Hamel, PP. (2010) C-type CytochromeAssembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome C1/Lyase Interaction. Genetics, 186 (2) 561-71.
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.
Thesis
- Mathieu, L. (2009) La biogénèse des complexes respiratoires mitochondriaux chez la levure Saccharomyces cerevisiae. Université de Versailles - Saint-Quentin-en-Yvelines. Direction de thèse : G. Dujardin.
- Nouet, C. (2008) Biogenèse des complexes respiratoires mitochondriaux chez la levure Saccharomyces cerevisiae et les cellules humaines. Université Versailles Saint-Quentin. Direction de thèse : G. Dujardin
In progress
- Ostojic, J. (soutenance prévue en 2013) Contrôle de l’assemblage des complexes respiratoires mitochondriaux. Université Evry-Val d’Essonne. Direction de thèse : G. Dujardin.
- Vallières, C. (soutenance prévue 2012) Etude du développement de la résistance aux agents antimicrobiens ciblant le complexe III de la chaîne respiratoire mitochondriale, en utilisant la levure comme système modèle. Université Paris Sud-Orsay. Direction de thèse : B. Meunier.
