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 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.
Mironova
Galina D
GD
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region 142290, Russia. mironova@iteb.ru
Gritsenko
Elena
E
Gateau-Roesch
Odile
O
Levrat
Christiane
C
Agafonov
Alexey
A
Belosludtsev
Konstantin
K
Prigent
Annie France
AF
Muntean
Danina
D
Dubois
Madeleine
M
Ovize
Michel
M
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005354:Fibrosarcoma / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D051379:Mice; D008930:Mitochondria, Liver; D009997:Osmotic Pressure; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014882:Water-Electrolyte Balance
D008081:Liposomes; D008567:Membranes, Artificial; D019308:Palmitic Acid; D016572:Cyclosporine; D002118:Calcium