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

• Authors: Kersti Tepp , Natalja Timohhina , Vladimir Chekulayev , Igor Shevchuk , Tuuli Kaambre , Valdur Saks
• Languages of publication: EN

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.

Keywords

EN

cardiomyocytes; creatine kinase; metabolic control analysis; respiration; mitochondria

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2010
• Volume: 57
• Issue: 4
• Pages: 421-430

Dates

published

2010

received

2010-08-31

revised

2010-12-09

accepted

2010-12-16

(unknown)

2010-12-18

Contributors

author

Kersti Tepp

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

author

Natalja Timohhina

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

author

Vladimir Chekulayev

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

author

Igor Shevchuk

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

author

Tuuli Kaambre

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

author

Valdur Saks

• Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

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