title: MECHANISMS OF INTEGRATION AND REGULATION OF MITOCHONDRIA AND ATPASES IN NORMAL AND DISEASED OXIDATIVE MUSCLE CELL
reg no: SF0182606s03
project type: postdoctor targeted financing
subject: 1.6-1.9. Chemistry and Molecular Biology
3. Medical Sciences
institution: University of Tartu
name: Enn Seppet
description: As a result of previous project financed by Estonian Ministry of Education we have proposed a new concept which describes the supramolecular organization of energy metabolism - intracellular energetic units (ICEU), which exist in oxidative muscle cells and represent the complexes of mitochondria with sarcomeric and sarcoplasmic reticular ATPases (Seppet et al., BBA,2001;1504:379-395; Saks et al., Biochem J, 2001;356:643-657). Within the ICEU the energy produced by mitochondria is transferred to ATPases by creatine and adenylate kinases, and by direct transfer of ATP. The aim of the present project is to solve the following problems in relation to structure and function of ICEU: 1) To define the nature and role of the structural proteins of ICEU in fixation of intracellular positioning of mitochondria; 2) to reveal the dependence of regulation of oxidative phosphorylation on intracellular calcium level and means of the energy transfer under different workloads and energy fluxes (studies on the mechanisms of Starling's phenomenon in frames of the ICEU); 3) to reveal the mechanisms of structural and functional alterations in ICEU, in the processes of apoptosis, cardiac failure and myopathies. To accomplish these tasks, the molecular biological, physiological, biophysical methods together with mathematical modelling, that allow to analyse the energy metabolism in relation to contractile function of muscle cell, will be used. The results will give a new information regarding the mechanisms of organization and regulation of energy metabolism in muscle cells in vivo, in normal and pathological states.

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