title: Formation of palmitic acid/Ca2+ complexes in the mitochondrial membrane: a possible role in the cyclosporin-insensitive permeability transition.
abstract: 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.
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region 142290, Russia. mironova@iteb.ru
authors.forename: Galina D
authors.initials: GD
authors.lastname: Mironova
authors.forename: Elena
authors.initials: E
authors.lastname: Gritsenko
authors.forename: Odile
authors.initials: O
authors.lastname: Gateau-Roesch
authors.forename: Christiane
authors.initials: C
authors.lastname: Levrat
authors.forename: Alexey
authors.initials: A
authors.lastname: Agafonov
authors.forename: Konstantin
authors.initials: K
authors.lastname: Belosludtsev
authors.forename: Annie France
authors.initials: AF
authors.lastname: Prigent
authors.forename: Danina
authors.initials: D
authors.lastname: Muntean
authors.forename: Madeleine
authors.initials: M
authors.lastname: Dubois
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: 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
chemical_list: D008081:Liposomes; D008567:Membranes, Artificial; D019308:Palmitic Acid; D016572:Cyclosporine; D002118:Calcium