Magnesium ion modulates the sensitivity of the mitochondrial permeability transition pore to cyclosporin A and ADP.
Magnesium ion modulates the sensitivity of the mitochondrial permeability transition pore to cyclosporin A and ADP.
复制标题
镁离子调节线粒体通透性转换孔对环孢菌素 A 和 ADP 的敏感性。
DOI：
10.1006/abbi.1994.1230
复制
发表时间：
1994
影响因子：
3.9
通讯作者：
Pfeiffer,DR
中科院分区：
文献类型：
--
作者：
Novgorodov,SA;Gudz,TI;Brierley,GP;Pfeiffer,DR
Regulation of the mitochondrial permeability transition pore has been investigated following the release of matrix solutes which normally participate in pore regulation. Under these conditions, neither cyclosporin A nor ADP induces pore closure, as judged by restoration of Δ Ψ, unless Mg2+is also added. Mg2+alone is ineffective. In liver mitochondria, the Mg2+effect is expressed over a 0 to 0.5 mM concentration range with higher concentrations inhibiting repolarization. In heart mitochondria, the inhibitory action of high Mg2+is not seen and it can be shown that the Mg2+effect on repolarization increases progressively up to a concentration of 5 mM. In liver mitochondria, when the pore is closed by maximally effective concentrations of Mg2+plus cyclosporin A or Mg2+plus ADP, reopening occurs upon the addition of carboxyatractyloside. The latter compound, however, fails to reopen the pore when Mg2+, cyclosporin A, and ADP are present simultaneously. In heart mitochondria, where higher Mg2+concentrations can be employed, Mg2+plus cyclosporin A or Mg2+plus ADP produces pore closure in a carboxyatractyloside insensitive manner. Titration experiments support the adenine nucleotide translocase as the site at which carboxyatractyloside acts to regulate the pore. However, the action of ADP appears to involve a translocase-independent site. In intact mitochondria the action of carboxyatractyloside on pore opening is counteracted by oligomycin, apparently through inhibition of the F1F0ATP synthase, with a consequent increase in the matrix space ADP/ATP ratio. It is concluded that the permeability transition pore induced by Ca2+plusPiis not formed from the adenine nucleotide translocase although the translocase conformation is one of several factors which regulate the pore. The matrix Mg2+concentration is also one of these factors. Formation of the pore by a Ca2+and ADP binding protein is one model which is consistent with the present data.
