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Reconstituted adenine nucleotide translocase forms a channel for small molecules comparable to the mitochondrial permeability transition pore
Author(s) -
Rück Alexander,
Dolder Max,
Wallimann Theo,
Brdiczka Dieter
Publication year - 1998
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(98)00317-2
Subject(s) - mitochondrial permeability transition pore , voltage dependent anion channel , ant , liposome , translocase , atp–adp translocase , porin , biophysics , mitochondrion , adenine nucleotide translocator , chemistry , biochemistry , cardiolipin , hexokinase , vesicle , inner mitochondrial membrane , adenine nucleotide , permeability (electromagnetism) , nucleotide , biology , membrane , metabolism , bacterial outer membrane , glycolysis , phospholipid , apoptosis , ecology , chromosomal translocation , escherichia coli , programmed cell death , gene
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 Ca 2+ concentrations could be demonstrated. N ‐Methyl‐Val‐4‐cyclosporin did not inhibit the Ca 2+ 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 HgCl 2 (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.