Long‐chain fatty acids promote opening of the reconstituted mitochondrial permeability transition pore

FEBS Letters

Brdiczka, Dieter¹  Wojtczak, Lech²  Wiȩckowski, Mariusz R.² 

[1]Faculty of Biology, University of Konstanz, D-78434 Konstanz, Germany

[2]Nencki Institute of Experimental Biology, Pasteura 3, PL-02-093 Warsaw, Poland

关键词: Mitochondrial permeability transition pore;    Reconstitution;    Fatty acid;    Hexokinase;    Phospholipase A2;    ANT;    adenine nucleotide translocase;    PTP;    mitochondrial permeability transition pore;    Δψ;    mitochondrial transmembrane electric potential;   

DOI  :  10.1016/S0014-5793(00)02127-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Ca²⁺ 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 Ca²⁺ 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 A₂. 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].

【 授权许可】

Unknown