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Long‐chain fatty acids promote opening of the reconstituted mitochondrial permeability transition pore
Author(s) -
Wiȩckowski Mariusz R.,
Brdiczka Dieter,
Wojtczak Lech
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02127-x
Subject(s) - mitochondrial permeability transition pore , vesicle , phospholipid , protonophore , chemistry , fatty acid , biochemistry , permeability (electromagnetism) , phospholipase a2 , liposome , biophysics , myristic acid , phosphatidylcholine , mitochondrion , membrane , palmitic acid , biology , enzyme , apoptosis , programmed cell death
Adenine nucleotide translocase–porin–hexokinase complex isolated from rat brain, when reconstituted into phospholipid‐cholesterol vesicles, exhibits all properties of the mitochondrial permeability transition pore [Beutner, G., Rück, A., Riede, B., Welte, W. and Brdiczka, D. (1996) FEBS Lett. 396, 189–195]. In the present work, the effect of long‐chain fatty acids on such reconstituted pore was examined. Opening of the pore was measured by leakage of either malate or fluorescein sulphonate entrapped inside the vesicles. It was found that myristate and oleate in the presence of 50 or 100 μM Ca 2+ produced a partial release of the probes in a dose‐dependent way. A dicarboxylic fatty acid analogue, that appeared inactive as protonophore in intact mitochondria, exerted no effect on pore opening in the reconstituted system. 100 μM Ca 2+ alone was without effect. Pore opening by fatty acids in the reconstituted system was partly prevented by cyclosporin A. The pore opening also occurred when the vesicles were incubated in the presence of pancreatic phospholipase A 2 . In this case, the opening was decreased by cyclosporin A or serum albumin. These results indicate that long‐chain fatty acids elicit opening of the permeability transition pore reconstituted in phospholipid vesicles in a similar way as in intact mitochondria [Wiȩckowski, M.R. and Wojtczak, L. (1998) FEBS Lett. 423, 339–342].