Korotkov , S M , Konovalova , S A , Brailovskaya , I V & Saris , N-E L 2016 , ' To involvement the conformation of the adenine nucleotide translocase in opening the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria ' , Toxicology in Vitro , vol. 32 , pp. 320-332 . https://doi.org/10.1016/j.tiv.2016.01.015
Title: | To involvement the conformation of the adenine nucleotide translocase in opening the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria |
Author: | Korotkov, Sergey M.; Konovalova, Svetlana A.; Brailovskaya, Irina V.; Saris, Nils-Erik L. |
Contributor organization: | Department of Food and Nutrition |
Date: | 2016-04 |
Language: | eng |
Number of pages: | 13 |
Belongs to series: | Toxicology in Vitro |
ISSN: | 0887-2333 |
DOI: | https://doi.org/10.1016/j.tiv.2016.01.015 |
URI: | http://hdl.handle.net/10138/233305 |
Abstract: | The conformation of adenine nucleotide translocase (ANT) has a profound impact in opening the mitochondrial permeability transition pore (MPTP) in the inner membrane. Fixing the ANT in 'c' conformation by phenylarsine oxide (PAO), tert-butylhydroperoxide (tBHP), and carboxyatractyloside as well as the interaction of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) with mitochondrial thiols markedly attenuated the ability of ADP to inhibit the MPTP opening. We earlier found (Korotkov and Saris, 2011) that calcium load of rat liver mitochondria in medium containing TINO3 and KNO3 stimulated the Tl+-induced MPTP opening in the inner mitochondrial membrane. The MPTP opening as well as followed increase in swelling, a drop in membrane potential (Delta Psi(mito)), and a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration were visibly enhanced in the presence of PAO, tBHP, DIDS, and carboxyatractyloside. However, these effects were markedly inhibited by ADP and membrane-penetrant hydrophobic thiol reagent, N-ethylmaleimide (NEM) which fix the ANT in 'm' conformation. Cyclosporine A additionally potentiated these effects of ADP and NEM. Our data suggest that conformational changes of the ANT may be directly involved in the opening of the Tl+-induced MPTP in the inner membrane of Ca2+-loaded rat liver mitochondria. Using the Tl+-induced MPTP model is discussed in terms finding new transition pore inhibitors and inducers among different chemical and natural compounds. (C) 2016 Elsevier Ltd. All rights reserved. |
Subject: |
Tl+
Ca2+ Mitochondrial permeability transition Adenine nucleotide translocase conformation Mitochondrial swelling Rat liver mitochondria HEART-MITOCHONDRIA POTASSIUM CHANNELS THALLIUM TOXICITY SULFHYDRYL-GROUPS OXIDATIVE STRESS ION-TRANSPORT CYCLOPHILIN-D MEMBRANE PERMEABILIZATION LIPID-PEROXIDATION N-ETHYLMALEIMIDE 1182 Biochemistry, cell and molecular biology |
Peer reviewed: | Yes |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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