Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria.
Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria.
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发表时间：
1993-10
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通讯作者：
V. Petronilli;C. Cola;S. Massari;R. Colonna;P. Bernardi
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作者：
V. Petronilli;C. Cola;S. Massari;R. Colonna;P. Bernardi
本文报道了膜电位对线粒体通透性转换孔（MTP）的调节作用。在补充磷酸盐的蔗糖培养基中加载小Ca2+脉冲的通电大鼠肝线粒体由于高膜电位而有利于高MTP“闭合”概率，因此保持对蔗糖的低渗透性。去极化后，通过添加完全解偶联浓度的羰基氰化物对三氟甲氧基苯腙（FCCP）线粒体有利于高MTP的“开放”的概率，并迅速经历了一个过程的渗透膨胀后，蔗糖向基质扩散。用FCCP滴定表明，可能存在具有不同MTP开放门控电位的线粒体的离散亚群，因为FCCP浓度的增加增加使线粒体发生渗透性肿胀的分数增加。我们表明，生理效应（Ca2+，Mg2+，ADP，棕榈酸）修改孔开放的线粒体人口在任何给定的膜电位的功能开放孔的线粒体的分数转移。因此，许多诱导剂和抑制剂可以通过对MTP电压感测的影响直接影响孔，而不是通过对膜电位的影响间接影响孔。因此，许多效应物可通过将MTP门控电位转移至较高水平来诱导孔开放，而许多抑制剂可通过将MTP门控电位转移至较低水平来诱导孔闭合。
This paper reports an investigation on the modulation of the mitochondrial permeability transition pore (MTP) by the membrane potential. Energized rat liver mitochondria loaded with a small Ca2+ pulse in sucrose medium supplemented with phosphate favor a high MTP "closed" probability because of the high membrane potential and therefore maintain a low permeability to sucrose. Upon depolarization by the addition of fully uncoupling concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) mitochondria favor a high MTP "open" probability and rapidly undergo a process of osmotic swelling following sucrose diffusion toward the matrix. A titration with FCCP reveals that discrete subpopulations of mitochondria with different gating potentials for MTP opening may exist, since increasing concentrations of FCCP increase the fraction of mitochondria undergoing osmotic swelling. We show that physiological effectors (Ca2+, Mg2+, ADP, palmitate) modify pore opening in a mitochondrial population by shifting the fraction of mitochondria with a functionally open pore at any given membrane potential. Many inducers and inhibitors may therefore affect the pore directly through an effect on the MTP voltage sensing rather than indirectly through an effect on the membrane potential. Thus, many effectors may induce pore opening by shifting the MTP gating potential to higher levels, whereas many inhibitors may induce pore closure by shifting the MTP gating potential to lower levels.