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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Mitochondria;Permeability transition pore;Ca2+;NAD(P)H oxidation;SH-groups cross-linking;MTP;mitochondrial permeability transition pore;DQ;duroquinone;PhAsO;phenylarsine oxide;NEM;N-ethylmaleimide;EGTA;[ethylenebis(oxoethylene nitrilo)]tetraacetic acid;CCCP;carbonylcyanide-m-chloromethoxyphenyl hydrazone;CsA;cyclosporin A