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The results of recent research in our laboratories indicate that in oxidative muscle cells mitochondria, due to their strict interactions with cytoskeletal proteins, form functional complexes with myofibrils and sarcoplasmic reticulum. The main aim of the project is to develop these investigations and to study connections between different cellular macro- and microdomains of the ATP in these complexes by new approach combining optical techniques with targeted gene modification technologies of molecular biology. ATP microcompartmentation in the cells will be studied by using recombinant selectively targeted luciferase and selectively inactivated creatine kinase isoenzymes. The mitochondrial function and their regulation by intracellular communications in muscle cells will be studied in experimental models by using the permeabilized cell technique, by respirometry, spectrophotometry and HPLC analyses. The concentrations and channelling of adenine nucleotides in microcompartments in mitochondria, in myofibrils and at the cellular membranes and the complex intracellular structural and functional communications of mitochondria with other cellular structures will be investigated in normal cells and in conditions of preconditioning of the heart for its protection against ischemic damage. The results will be analysed by using the mathematical model of compartmentalized energy transfer. This project continues the traditional scientific collaboration between two Estonian laboratories and J.Fourier University in France, with addition of new international partner - the laboratory of Prof. Be Wieringa at the Nijmegen Center for Molecular Life Sciences, University of Nijmegen, The Netherlands. Thus, the project continues and develops the international cooperation in the European Research Space. |