Objectif
Oxidative phosphorylation (OXPHOS) is the metabolic process that provides most of the energy usable by the cells. OXPHOS couples two sets of reactions, respiration and ATP synthesis. Respiration consists in the sequential transfer of electrons carried out by the mitochondrial respiratory chain (MRC) complexes I (CI), II (CII), III (CIII), and IV (CIV). The proton gradient generated during respiration is used by the ATP synthase (CV). The components of the OXPHOS system, localized in the inner mitochondrial membrane, are large heteromeric enzymes whose subunits are encoded in two separated genomes, the nuclear and mitochondrial (mt) DNAs. The assembly of these subunits into the complete complexes is an intricate process in which many factors must interplay. In addition, it has been proved that CI, CIII and CIV interact with each other giving rise to supercomplexes (also called respirasomes). It has been determined that many mitochondrial disorders result in an altered assembly of one or several components of the MRC. However, many aspects of the mechanisms underlying the molecular defects in these disorders are still unknown. Therefore, it is necessary to investigate the assembly processes and the involved factors, in order to get a deeper understanding on OXPHOS biogenesis that will shed light on the pathogenetic mechanisms underlying the mitochondrial disorders caused by defective complex assembly. The objectives of the study will be: 1) to determine the entry point of the mtDNA-encoded CI subunits in the assembly process of this complex, which remains to be established; 2) to determine the order of events and the involved factors in the assembly process of human and mouse CIII which has not been studied yet in mammalian systems and 3) to study the factors and processes that determine the interaction between the individual complexes in the formation of the supercomplexes and the physiological relevance of these interactions for the activity of the OXPHOS system.
Champ scientifique
Appel à propositions
FP7-PEOPLE-ERG-2008
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Régime de financement
MC-ERG - European Re-integration Grants (ERG)Coordinateur
50009 Zaragoza
Espagne