Regulation of the inner membrane mitochondrial permeability transition by the outer membrane translocator protein (peripheral benzodiazepine receptor).
We studied the properties of the permeability transition pore (PTP) in rat liver mitochondria and in mitoplasts retaining inner membrane ultrastructure and energy-linked functions. Like mitochondria, mitoplasts readily underwent a permeability transition following Ca(2+) uptake in a process that maintained sensitivity to cyclosporin A. On the other hand, major differences between mitochondria and mitoplasts emerged in PTP regulation by ligands of the outer membrane translocator protein of 18 kDa, TSPO, formerly known as the peripheral benzodiazepine receptor. Indeed, (i) in mitoplasts, the PTP could not be activated by photo-oxidation after treatment with dicarboxylic porphyrins endowed with protoporphyrin IX configuration, which bind TSPO in intact mitochondria; and (ii) mitoplasts became resistant to the PTP-inducing effects of N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide and of other selective ligands of TSPO. Thus, the permeability transition is an inner membrane event that is regulated by the outer membrane through specific interactions with TSPO.
Department of Biomedical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Padova, I-35121 Padova, Italy.
Justina
J
Sileikyte
Valeria
V
Petronilli
Alessandra
A
Zulian
Federica
F
Dabbeni-Sala
Giuseppe
G
Tognon
Peter
P
Nikolov
Paolo
P
Bernardi
Fernanda
F
Ricchelli
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D004072:Digitonin / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D002352:Carrier Proteins; D011166:Porphyrins; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D004072:Digitonin; D002118:Calcium