Proton selective substate of the mitochondrial permeability transition pore: Regulation by the redox state of the electron transport chain
Proton selective substate of the mitochondrial permeability transition pore: Regulation by the redox state of the electron transport chain
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DOI：
10.1021/bi980820c
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发表时间：
1998-09-22
期刊：
影响因子：
2.9
通讯作者：
Pfeiffer, DR
中科院分区：
文献类型：
--
作者：
Broekemeier, KM;Klocek, CK;Pfeiffer, DR
螯合游离Ca ~（2+）可关闭大鼠肝线粒体的通透性转换孔，使大分子物质如甘露醇和蔗糖不能通过。然而，一个明显的H+传导基板在这些条件下仍然开放，所示的持久性的最大O-2消耗率和未能恢复膜电位。有利于闭孔的试剂，如环孢菌素A、ADP、Mg 2+或牛血清白蛋白，不关闭H+传导亚基，但当呼吸受到O-2的可用性限制时，它会自发关闭。封闭引起的O-2限制需要游离Mg 2+在亚微摩尔浓度范围内，并成为效率较低，随着时间的增加，在游离Ca 2+的存在下。的H+-传导substate显然是受电子传递链的氧化还原状态，减少有利于关闭的形式。支持孔与呼吸链复合物之一之间的物理缔合（或等效性）。这些特征表明，如果它涉及一小部分总线粒体，则这种转变在体内是不可逆的，并且会导致它们被细胞消除和/或替代。这一建议的影响被认为是，因为它们涉及到一个可能的作用，在细胞凋亡和消除线粒体含有突变的DNA的过渡。
The permeability transition pore of rat liver mitochondria can be closed by chelating free Ca2+, with respect to the passage of large molecules such as mannitol and sucrose. However, an apparent H+-conducting substrate remains open under these conditions, as indicated by the persistence of maximal O-2 consumption rates and by the failure to recover a membrane potential. Agents which favor a closed pore, such as cyclosporin A, ADP, Mg2+, or bovine serum albumin, do not close the H+-conducting substate, but it closes spontaneously when respiration becomes limited by the availability of O-2. Closure provoked by an O-2 limitation requires free Mg2+ in the sub-micromolar concentration range and becomes less efficient with increasing time spent in the presence of free Ca2+. The H+-conducting substate is apparently regulated by the redox status of the electron transport chain, with a reduced form favoring closure. A physical association (or equivalence) between the pore and one of the respiratory chain complexes is supported. These characteristics suggest that the transition is irreversible in vivo, if it involves a small fraction of total mitochondria, and would lead to their elimination and/or replacement by the cell. The implications of this proposal are considered, as they relate to a possible role for the transition in cellular apoptosis and the elimination of mitochondria containing mutated DNA.