Intracellular energetic units in healthy and diseased hearts.
BACKGROUND
The present review examines the role of intra-cellular compartmentation of energy metabolism in vivo.


OBJECTIVE
To compare the kinetics of the activation of mitochondrial respiration in skinned cardiac fibres by exogenous and endogenous adenine nucleotides in dependence of the modulation of cellular structure and contraction.


METHODS
Saponin-permeabilized cardiac fibres or cells were analyzed using oxygraphy and confocal microscopy.


RESULTS
Mitochondria respiration in fibres or cells was upregulated by cumulative additions of ADP to the medium with an apparent K(m) of 200 muM to 300 muM. When respiration was stimulated by endogenous ADP produced by intracellular ATPases, a near maximum respiration rate was achieved at an ADP concentration of less than 20 muM in the medium. A powerful ADP-consuming system, consisting of pyruvate kinase and phosphoenolpyruvate, that totally suppressed the activation of respiration by exogenous ADP, failed to abolish the stimulation of respiration by endogenous ADP, but did inhibit respiration after the cells were treated with trypsin. The addition of up to 4 muM of free Ca(2+) to the actively respiring fibres resulted in reversible hypercontraction associated with a decreased apparent K(m) for exogenous ADP. These changes were fully abolished in fibres after the removal of myosin by KCl treatment.


CONCLUSIONS
Mitochondria and ATPases, together with cytoskeletal proteins that establish the structural links between mitochondria and sarcomeres, form complexes - intracellular energetic units (ICEUs) - in cardiac cells. Within the ICEUs, the mitochondria and ATPases interact via specialized energy transfer systems, such as the creatine kinase- and adenylate kinase-phosphotransfer networks, and direct ATP channelling. Disintegration of the structure and function of ICEUs results in dyscompartmentation of adenine nucleotides and may represent a basis for cardiac diseases.
Seppet
Enn K
EK
Departments of Pathophysiology and Human Genetics and Biology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, University of Tartu, Tartu;
Eimre
Margus
M
Anmann
Tiia
T
Seppet
Evelin
E
Peet
Nadezhda
N
Käämbre
Tuuli
T
Paju
Kalju
K
Piirsoo
Andres
A
Kuznetsov
Andrei V
AV
Vendelin
Marko
M
Gellerich
Frank N
FN
Zierz
Stephan
S
Saks
Valdur A
VA