Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient. Evidence that the pore can be opened by membrane depolarization.
Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient. Evidence that the pore can be opened by membrane depolarization.
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DOI：
10.1016/s0021-9258(19)50355-6
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发表时间：
1992-05
期刊：
影响因子：
--
通讯作者：
P. Bernardi
中科院分区：
文献类型：
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作者：
P. Bernardi
本文研究了大鼠肝脏线粒体中质子电化学梯度（δ mu H+）与环孢素a敏感渗透过渡孔（PTP）的关系。以SH基团交联剂氧化苯larsin为诱导剂，我们发现基质pH和膜电位都可以独立于Ca2+调节PTP的诱导过程。我们发现，当pHi大于7.0时，膜去极化诱导PTP本身，而在酸性基质pH值下，PTP的诱导被有效阻止。由于Ca2+摄取导致δ mu H+的主要修饰（即基质碱化和膜去极化），我们已经探索了Ca（2+）诱导的δ mu H+变化可能有助于Ca2+诱导PTP的可能性。我们在Ca2+ + n -乙基马来酰亚胺和Ca2+ +磷酸处理的线粒体中的数据表明，膜去极化是PTP的强大诱导剂。综上所述，我们的观察结果表明，在Ca2+存在和不存在的情况下，PTP都可以直接由δ mu H+控制，并表明在许多实验条件下，膜电位的崩溃可能是PTP诱导的原因而不是结果。因此，许多诱导剂可能通过各种机制聚集在δ H+的膜电位分量的耗散上。
This paper reports an investigation on the relationship between the proton electrochemical gradient (delta mu H+) and the cyclosporin A-sensitive permeability transition pore (PTP) in rat liver mitochondria. Using the SH group cross-linker phenylarsine oxide as the inducer, we show that both matrix pH and the membrane potential can modulate the process of PTP induction independently of Ca2+. We find that membrane depolarization induces the PTP per se when pHi is above 7.0, while at acidic matrix pH values PTP induction is effectively prevented. Since Ca2+ uptake leads to major modifications of the delta mu H+ (i.e. matrix alkalinization and membrane depolarization), we have explored the possibility that the Ca(2+)-induced changes of the delta mu H+ may contribute to PTP induction by Ca2+. Our data in mitochondria treated with Ca2+ plus N-ethylmaleimide and Ca2+ plus phosphate show that membrane depolarization is a powerful inducer of the PTP. Taken together, our observations indicate that the PTP can be controlled directly by the delta mu H+ both in the absence and presence of Ca2+, and suggest that a collapse of the membrane potential may be the cause rather than the consequence of PTP induction under many experimental conditions. Thus, many inducers may converge on dissipation of the membrane potential component of the delta mu H+ by a variety of mechanisms.