The translocator protein (peripheral benzodiazepine receptor) mediates rat-selective activation of the mitochondrial permeability transition by norbormide

Biochimica Et Biophysica Acta
Alessandra ZulianFernanda Ricchelli

Abstract

We have investigated the mechanism of rat-selective induction of the mitochondrial permeability transition (PT) by norbormide (NRB). We show that the inducing effect of NRB on the PT (i) is inhibited by the selective ligands of the 18kDa outer membrane (OMM) translocator protein (TSPO, formerly peripheral benzodiazepine receptor) protoporphyrin IX, N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide and 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one; and (ii) is lost in digitonin mitoplasts, which lack an intact OMM. In mitoplasts the PT can still be induced by the NRB cationic derivative OL14, which contrary to NRB is also effective in intact mitochondria from mouse and guinea pig. We conclude that selective NRB transport into rat mitochondria occurs via TSPO in the OMM, which allows its translocation to PT-regulating sites in the inner membrane. Thus, species-specificity of NRB toward the rat PT depends on subtle differences in the structure of TSPO or of TSPO-associated proteins affecting its substrate specificity.

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Citations

Aug 13, 2013·BioMed Research International·Franklin C WongDean F Wong
Dec 19, 2012·Molecular and Cellular Endocrinology·Leeyah IssopVassilios Papadopoulos
Apr 29, 2015·Oxidative Medicine and Cellular Longevity·Lukas J MotlochFadi G Akar
Oct 11, 2016·Frontiers in Pharmacology·Claudio D'AmoreSergio Bova
Jun 14, 2019·Oxidative Medicine and Cellular Longevity·Justina Šileikytė, Michael Forte
Jan 13, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Erik NutmaBenjamin B Tournier
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Felipe Salazar-RamírezGerardo García-Rivas

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