Projet ANR-07-BLAN-0360 – MITOPULSE : MITOPULSE
Programme : Blanc (BLANC) 2007
Année de financement : 2007
Coordinateur du projet : Monsieur Fabrice RAPPAPORT (CNRS DELEGATION REGIONALE PARIS B)
Partenaires : Centre national de la recherche scientifique; Centre national de la recherche scientifique
Montant : 388400.0 euros
Date de début : 2008
Durée : 48 mois
Résumé : The mitochondria and chloroplast are the power-houses of eukaryotic cells. They are both in charge of the efficient provision of energy by feeding metabolism with its major substrate: ATP. The oxidative-phosphorylation system, described by Mitchell, relies on the generation, by an electron/proton transfer chain, of an electrochemical transmembrane potential utilized to synthesize ATP. Beside this functional analogy, these two systems also share ultrastuctural similarities, the two chains being embedded in a membrane which is characterized by an intricate architecture. Despite these similarities, the current knowledge of the function of the photosynthetic chain is more refined than that of its respiratory counterpart. This likely stems from the fact that, in the photosynthetic case, the substrate, a photon, can be delivered accurately under the form of flashes. This constitutes, from an experimental stand-point, a considerable advantage since it allows triggering the whole chain with almost no limitation to the time resolution. Besides the accuracy in the understanding of the function of the photosynthetic process, functional studies have recently pinpointed the importance of the association of the enzymes into 'super-complexes' as well as the consequences of the peculiar membrane topology on the function of the chain. Although the fundamental principles enounced by Mitchell still apply, the emerging picture of the photosynthetic chain clearly diverges from the linear and fluid scheme, and the common thinking is that the overall properties of the chain cannot be described by the simple combination of the individual properties of its component. -  Recent results have suggested that this also applies to the respiratory chain. Evidences that mitochondrial electron transfer complexes specifically interact to form supramolecular structures come from works on Saccharomyces cerevisiae, beef and plants. Recently, the functional complementation of two defective respiratory chains by cell fusion has shown that the recovery of the respiratory activity correlates with the abundance of supercomplexes including complexes III and IV, suggesting that supercomplex assembly is a necessary step for respiration. Yet, the understanding of the role of these supramolecular assemblies is still lacking. -  Supercomplexes are not the only ultra-structural motives susceptible to play an important role in controlling the overall oxidative phosphorylation activity of the respiratory chain in organelles. 3D images provided by tomography suggest that the internal membrane in mitochondria might be compartmented, and that diffusion between these internal compartments might be restricted. There is considerable evidences that the mitochondrial inner membrane is a dynamic structure able to change shape rapidly in response to alterations in osmotic or metabolic conditions. If cristae morphology can indeed regulate rates of chemiomosmis, such structural impact could be part of an integral feed back mechanism by which mitochrondria respond to environmental perturbations. -  Mitochondrial oxidative phosphorylation is fundamental in all aspects of cellular life in aerobic cells and organisms. The constant requirement in energy to maintain the cell metabolism is a demanding task for the mitochondria. Respiratory chain defects are associated with an increasing group of human diseases and with a wide range of clinical symptoms. Yet, the causality link between mutations, respiratory defects and associated phenotypes remains obscure. -  The aim of the project is to unravel the functional consequences of the peculiar biochemical and membrane structures in mitochondria and to assess the consequences of mutations on the respiratory chain function. We will develop tools to monitor in vivo, in intact cells, electron transfer through the respiratory enzymes and to characterize the functional consequences of the ultra-structure of the respiratory chain on the respiratory activity