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2010 | 57 | 4 | 421-430
Article title

Metabolic control analysis of integrated energy metabolism in permeabilized cardiomyocytes - experimental study

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Abstracts
EN
The main focus of this research was to apply Metabolic Control Analysis to quantitative investigation of the regulation of respiration by components of the Mitochondrial Interactosome (MI, a supercomplex consisting of ATP Synthasome, mitochondrial creatine kinase (MtCK), voltage dependent anion channel (VDAC), and tubulin) in permeabilized cardiomyocytes. Flux control coefficients (FCC) were measured using two protocols: 1) with direct ADP activation, and 2) with MtCK activation by creatine (Cr) in the presence of ATP and pyruvate kinase-phosphoenolpyruvate system. The results show that the metabolic control is much stronger in the latter case: the sum of the measured FCC is 2.7 versus 0.74 (ADP activation). This is consistent with previous data showing recycling of ADP and ATP inside the MI due to the functional coupling between MtCK and ANT and limited permeability of VDAC for these compounds, PCr being the major energy carrier between the mitochondria and ATPases. In physiological conditions, when the MI is activated, the key sites of regulation of respiration in mitochondria are MtCK (FCC = 0.93), adenine nucleotide translocase ANT (FCC = 0.95) and CoQ cytochrome c oxidoreductase (FCC = 0.4). These results show clearly that under the physiological conditions the energy transfer from mitochondria to the cytoplasm is regulated by the MI supercomplex and is very sensitive to metabolic signals.
Publisher

Year
Volume
57
Issue
4
Pages
421-430
Physical description
Dates
published
2010
received
2010-08-31
revised
2010-12-09
accepted
2010-12-16
(unknown)
2010-12-18
Contributors
author
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
author
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
author
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
author
  • Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv57p421kz
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