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Our previous project financed by ESF (Grant No 3637) resulted in a new hypothesis, according to which the mitochondria form complexes with ATPases (called by us as the intracellular energetic units -ICEUs)in oxidative muscle cells, which provide the means for effective energy transduction and feedback between these structures (Seppet et al., BBA, 2001;1504:379-395; Saks et al., Biochem J, 2001; 356:643-657). The present project is aimed to reveal the molecular and supramolecular structure and function of the ICEU, depending on the contractile activity, stage of postnatal development and expression of proteins specific for the oxidative muscle cells. The results expected are as following: a) It will be demonstrated that at least some of the proteins expressed exclusively in oxidative muscles, are able to link the mitochondria to the ATPases, as well as to compartmentalize a fraction of cellular adenine nucleotides into the ICEU, thereby restricting their diffusion into the milieu (i.e. the cytoplasm) surrounding the ICEU. Therefore, the processes of energy transfer and feedback inside the ICEU become dependent on the local concentrations of adenine nucleotides which can integrate the mitochondria and ATPases directly and/or via the creatine kinase and adenylate kinase systems within this small fraction of intracellular space. b) The relative role of each of that process and their kinetic parameters will be described in dependence on the muscle contractile activity (length of sarcomere), which will be varied by altering the intracellular Ca2+ content. c) The conditions determining the formation and blocking of the mitochondrial permeability transition pore within ICEU will be characterized. d) It will be demonstrated that both the expression of proteins - the components of ICEU, its formation and the mode of energy transfer is subjected to postnatal control. e) The differences in ICEU function between distinct phenotypes of oxidative muscles will be outlined. f) On the basis of the results, the mathematical models of muscle energy metabolism previously elaborated by our laboratories will be further developed. |