Formation of palmitic acid/Ca2+ complexes in the mitochondrial membrane: a possible role in the cyclosporin-insensitive permeability transition

A possible role of palmitic acid/Ca2+ (PA/Ca2+) complexes in the cyclosporin-insensitive permeability transition in mitochondria has been studied. It has been shown that in the presence of Ca2+, PA induces a swelling of mitochondria, which is not inhibited by cyclosporin A. The swelling is accompani...

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Published in:Journal of bioenergetics and biomembranes 2004-04, Vol.36 (2), p.171-178
Main Authors: Mironova, Galina D, Gritsenko, Elena, Gateau-Roesch, Odile, Levrat, Christiane, Agafonov, Alexey, Belosludtsev, Konstantin, Prigent, Annie France, Muntean, Danina, Dubois, Madeleine, Ovize, Michel
Format: Article
Language:English
Subjects:
Animals
Calcium - chemistry
Calcium - metabolism
Cell Line, Tumor
Cell Membrane Permeability
Cells, Cultured
Cyclosporine - pharmacology
Fibrosarcoma - metabolism
Glioma - metabolism
Heart attacks
Intracellular Membranes - metabolism
Lipids
Liposomes - chemistry
Membranes
Membranes, Artificial
Mice
Mitochondria
Mitochondria, Liver
Myocardial infarction
Osmotic Pressure
Palmitic Acid - chemistry
Palmitic Acid - metabolism
Permeability
Rats
Water-Electrolyte Balance
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Summary:A possible role of palmitic acid/Ca2+ (PA/Ca2+) complexes in the cyclosporin-insensitive permeability transition in mitochondria has been studied. It has been shown that in the presence of Ca2+, PA induces a swelling of mitochondria, which is not inhibited by cyclosporin A. The swelling is accompanied by a drop in membrane potential, which cannot be explained only by a work of the Ca2+ uniporter. With time, the potential is restored. Evidence has been obtained indicating that the specific content of mitochondrial lipids would favor the PA/Ca2+ -induced permeabilization of the membrane. In experiments with liposomes, the PA/Ca2+ -induced membrane permeabilization was larger for liposomes formed from the mitochondrial lipids, as compared to the azolectin liposomes. Additionally, it has been found that in mitochondria of the TNF (tumor necrosis factor)-sensitive cells (WEHI-164 line), the content of PA is larger than in mitochondria of the TNF-insensitive cells (C6 line), with this difference being mainly provided by PA incorporated in phosphatidylethanolamine and especially, cardiolipin. The PA/Ca2+ -dependent mechanism of permeability transition in mitochondria might be related to some pathologies, e.g. myocardial ischemia. The heaviness of myocardial infarction of ischemic patients has been demonstrated to correlate directly with the content of PA in the human blood serum.
ISSN:0145-479X
1573-6881
DOI:10.1023/B:JOBB.0000023620.42653.b7