CORDIS provides links to public deliverables and publications of HORIZON projects.
Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .
Exploitable results
The results of the use of permeabilized cell and skinned fibre techniques and their applications for studies of mitochondrial function in vivo, obtained in four countries were analysed and summarised. Permeabilized cell and skinned fibre techniques have been shown to have several very significant advantages for studies of mitochondrial function, in comparison with traditional methods of use of isolated mitochondria: 1) very small tissue samples are required; 2) all cellular population of mitochondria can be investigated; 3) most important, however, is that mitochondria are studied in their natural environment. Kinetic studies of in vivo regulation of mitochondrial respiration by ADP in the cells showed that the kinetics of respiration regulation in muscle cells is tissue specific: we found that while in rat cardiac and soleus muscle fibers the apparent Km for respiration regulation was 300-500 µM and decreased to 50-80 µM in the presence of creatine, in skinned fibres from m. gastrocneminus and also from m. plantaris and m. quadriceps its value was initially very low, being equal to 10-20 µM, not different from that for isolated muscle mitochondria, and the effect of creatine was not observable under these experimental conditions. These results are taken to show that in cardiac and slow twitch skeletal muscle permeability of outer mitochondrial membrane for adenine nucleotides is low and controlled by some cytoplasmic protein sensitive to trypsin and chymotrypsin. Studies of desmin deficient transgenic mice that showed desmin itself does not display this type of control of mitochondrial porin pores, but its absence results in appearance of cells with disorganised structure and of altered mitochondrial population probably lacking this unknown VDAC controlling protein. The mathematical model of the compartmentalised energy transfer system in cardiac myocytes was created and used for interpretation of novel experimental data obtained by using phosphorus NMR for determination of the energy fluxes in the isolated hearts of transgenic mice with knocked out creatine kinase isoenzymes. The analysis of energy fluxes between different cellular compartments shows that in all cellular compartments of working heart cells the creatine kinase reaction is far from equilibrium in the systolic phase of the contraction cycle and approaches equilibrium only in cytoplasm and only in the end - diastolic phase of the contraction cycle. The model showed also that in the PCr pathway of intracellular energy transport two isoenzymes of creatine kinase always function in a co-ordinated manner out of equilibrium, in the steady state, and disturbances in functioning of one of them inevitably result in the disturbances of the other component of the PCr pathway. The studies of hypoxic and ischemic hearts by NMR method and skinned fibre technique showed that the most sensitive system to ischemic damages is the mitochondrial outer membrane - intermembrane compartment. The compartmentation of substrates should be accounted for in explaining the kinetics of energy transfer in the hypoxic hearts.
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