Ca2+-triggered membrane permeability transition in deenergized mitochondria from rat liver

Abstract
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 ‘Ca2+‐sensor’ that regulates the permeability transition pore opening.