Reconstituted adenine nucleotide translocase forms a channel for small molecules comparable to the mitochondrial permeability transition pore

FEBS Letters

Rück, Alexander²  Dolder, Max¹  Wallimann, Theo¹  Brdiczka, Dieter² 

[1] Institute for Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland;Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany

关键词: Adenine nucleotide translocase;    Mitochondrial permeability transition pore;    Porin;    Creatine kinase;    Hexokinase;    ANT;    adenine nucleotide translocase;    MTP;    mitochondrial permeability transition pore;    CsA;    cyclosporin A;    CyP D;    mitochondrial cyclophilin;    PAGE;    polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(98)00317-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Highly purified adenylate translocase (ANT) from rat heart mitochondria was functionally reconstituted as ATP/ADP exchange carrier in asolectin/cardiolipin vesicles. The ANT preparations used were free of porin, cyclophilin D, and Bax as analysed immunologically and by activity measurements. After pre-loading the ANT-containing proteoliposomes with ATP, malate or AMP, a gradual release of the trapped compounds by increasing the external Ca²⁺ concentrations could be demonstrated. N-Methyl-Val-4-cyclosporin did not inhibit the Ca²⁺ dependent release of internal substances from ANT liposomes. This inhibitor was found to be specific for the mitochondrial permeability transition pore (MTP) in intact mitochondria or reconstituted MTP-like protein complexes (e.g. hexokinase, porin, ANT complex). However, ADP in concentrations >20 μM inhibited the liberation of internal compounds, while in contrast, atractyloside (30 μM) and HgCl₂ (5 μM) both induced permeability of the ANT-containing liposomes resulting in a release of trapped substances. These results strongly suggest that ANT itself is capable to adopt a pore-like structure under conditions known to induce the permeability transition in mitochondria.

【 授权许可】

Unknown