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The Translocator Protein (Peripheral Benzodiazepine Receptor) Mediates Rat-Selective Activation of the Mitochondrial Permeability Transition by Norbormide

The Translocator Protein (Peripheral Benzodiazepine Receptor) Mediates Rat-Selective Activation of the Mitochondrial Permeability Transition by Norbormide

Alessandra Zulian, Justina Sileikytė, Valeria Petronilli, Sergio Bova, Federica Dabbeni-Sala, Gabriella Cargnelli, David Rennison, Margaret A Brimble, Brian Hopkins, Paolo Bernardi, Fernanda Ricchelli

Biochim Biophys Acta. 2011 Dec;1807(12):1600-5.

PMID: 21889488

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP142720249	N,N-Dihexyl-2-(4-fluorophenyl)indole-3-acetamide		142720-24-9	Price

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