Document Detail

Structure-function relationships in feedback regulation of energy fluxes in vivo in health and disease: mitochondrial interactosome.
MedLine Citation:
PMID:  20096261     Owner:  NLM     Status:  MEDLINE    
The aim of this review is to analyze the results of experimental research of mechanisms of regulation of mitochondrial respiration in cardiac and skeletal muscle cells in vivo obtained by using the permeabilized cell technique. Such an analysis in the framework of Molecular Systems Bioenergetics shows that the mechanisms of regulation of energy fluxes depend on the structural organization of the cells and interaction of mitochondria with cytoskeletal elements. Two types of cells of cardiac phenotype with very different structures were analyzed: adult cardiomyocytes and continuously dividing cancerous HL-1 cells. In cardiomyocytes mitochondria are arranged very regularly, and show rapid configuration changes of inner membrane but no fusion or fission, diffusion of ADP and ATP is restricted mostly at the level of mitochondrial outer membrane due to an interaction of heterodimeric tubulin with voltage dependent anion channel, VDAC. VDAC with associated tubulin forms a supercomplex, Mitochondrial Interactosome, with mitochondrial creatine kinase, MtCK, which is structurally and functionally coupled to ATP synthasome. Due to selectively limited permeability of VDAC for adenine nucleotides, mitochondrial respiration rate depends almost linearly upon the changes of cytoplasmic ADP concentration in their physiological range. Functional coupling of MtCK with ATP synthasome amplifies this signal by recycling adenine nucleotides in mitochondria coupled to effective phosphocreatine synthesis. In cancerous HL-1 cells this complex is significantly modified: tubulin is replaced by hexokinase and MtCK is lacking, resulting in direct utilization of mitochondrial ATP for glycolytic lactate production and in this way contributing in the mechanism of the Warburg effect. Systemic analysis of changes in the integrated system of energy metabolism is also helpful for better understanding of pathogenesis of many other diseases.
Valdur Saks; Rita Guzun; Natalja Timohhina; Kersti Tepp; Minna Varikmaa; Claire Monge; Nathalie Beraud; Tuuli Kaambre; Andrey Kuznetsov; Lumme Kadaja; Margus Eimre; Enn Seppet
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-01-21
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1797     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:    2010 Jun-Jul
Date Detail:
Created Date:  2010-06-21     Completed Date:  2011-01-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  678-97     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Laboratory of Fundamental and Applied Bioenergetics, INSERM U884, Joseph Fourier University, Grenoble, France.
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MeSH Terms
Adenine Nucleotides / metabolism
Cell Respiration
Creatine Kinase, Mitochondrial Form / metabolism
Cytoskeleton / metabolism
Energy Metabolism
Feedback, Physiological
Mitochondria / metabolism*
Mitochondria, Heart / metabolism
Mitochondria, Muscle / metabolism
Models, Biological
Muscle Fibers, Skeletal / metabolism
Myocytes, Cardiac / metabolism
Phosphocreatine / metabolism
Tubulin / metabolism
Voltage-Dependent Anion Channels / metabolism
Reg. No./Substance:
0/Adenine Nucleotides; 0/Tubulin; 0/Voltage-Dependent Anion Channels; 67-07-2/Phosphocreatine; EC Kinase, Mitochondrial Form

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