Ca(2+)-triggered membrane permeability transition in deenergized mitochondria from rat liver.
The opening of the cyclosporin A-sensitive permeability transition pore (MTP) in deenergized mitochondria was induced only at millimolar Ca2+. Pretreatment of the mitochondria with 'inducers', such as duroquinone and phenylarsine oxide, allowed observing the pore opening at 0.01-0.1 mM Ca2+. Duroquinone caused a rapid (within 20 s) NAD(P)H oxidation which was followed by a slow (20 min) induction of the pore sensitive to low Ca2+. Phenylarsine oxide capable of cross-linking of vicinal SH-groups caused pore formation without the oxidation of NAD(P)H. The pore opening by both 'inducers' was prevented by N-ethylmaleimide. We propose that oxidation or cross-linking of critical dithiol(s) in membrane proteins increase the sensitivity of a putative 'Ca(2+)-sensor' that regulates the permeability transition pore opening.
Chernyak
B V
BV
A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russian Federation.
Dedov
V N
VN
Chernyak VYa
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats
D016227:Benzoquinones; D007473:Ion Channels; D016572:Cyclosporine; D002118:Calcium; C034257:duroquinone