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Rôle de la cytoarchitecture dans la signalisation énergétique du cœur de souris

Abstract : The cardiac cell function requires a large amount of energy and therefore needs a high efficiency of energetic production and energetic transfer. While the energy production depends on the intrinsic properties of the mitochondria, it appears that the efficiency of energetic transfers from the main producers (mitochondria) to consumers (ATPases) could be related to the specific architecture of the cardiomyocyte, which ensures a unique spatial organization of internal structures (mitochondria, sarcoplasmic reticulum, myofilaments). In order to reveal the role of mitochondrial network organization in cardiac energy metabolism, we studied the cellular architecture and the energetic signalling of cardiomyocytes in the process of maturation of the cytoarchitecture and in a model which exhibits a perturbation of the mitochondrial dynamics. The first part of this work, which was performed during postnatal development of the mouse, showed the perfect synchronisation between the establishment of the cytoarchitecture and the maturation of the transfer of energy by direct channelling of adenine nucleotides between mitochondria and ATPases. While this study provides an element which would demonstrate the involvement of cellular architecture in the efficiency of energy transfer, it also highlighted the very early maturation of the energetic system of the cell. Knowing that the mitochondria are an integral part of the cell architecture and that the mitochondrial network is controlled by fusion and fission mechanisms, the second step of this work consisted in investigating the involvement of mitochondrial dynamics in cardiomyocyte energetics. Our work has shown that a decrease in expression of OPA1, a protein responsible for mitochondrial fusion, leads to disruption of mitochondrial morphology which does not affect intrinsic mitochondrial function but affects the direct channelling of ATP and ADP between mitochondria and ATPases of the myofilaments. Overall, these results clearly demonstrate that energy transfer in cardiomyocytes strictly depends on specific cellular architecture.
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Submitted on : Wednesday, February 1, 2012 - 3:11:47 PM
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Jérôme Piquereau. Rôle de la cytoarchitecture dans la signalisation énergétique du cœur de souris. Médecine humaine et pathologie. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA114801⟩. ⟨tel-00665260⟩

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