Control of the mitochondrial permeability transition pore by high-affinity ADP binding at the ADP/ATP translocase in permeabilized mitochondria
Control of the mitochondrial permeability transition pore by high-affinity ADP binding at the ADP/ATP translocase in permeabilized mitochondria
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DOI：
10.1023/a:1005568630151
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发表时间：
2000-02-01
影响因子：
3
通讯作者：
Hunter, DR
中科院分区：
文献类型：
--
作者：
Haworth, RA;Hunter, DR
低水平的ADP结合在ADP/ATP移位酶引起的抑制的Ca 2+诱导的线粒体内膜的渗透性转变，当使用线粒体，已经经历了一个过渡的收缩试验测量。抑制作用被羧基苍术苷阻止，但被米酵酸增强，米酵酸增加了ADP抑制作用的亲和力。这表明抑制作用与转位酶的构象有关。计算Ca 2+添加以去除大部分游离ADP。在ADP后加入Ca ~（2+），抑制作用衰减缓慢，这可能反映了ADP与转运体的解离。我们的结论是，形成一个渗透性转换孔（PTP）的概率是更大的时候，易位酶是在CAT构象比在BKA构象，并且，在没有CAT和BKA，易位之间的BKA和CAT构象的ADP结合和去除，即使在断电线粒体没有核苷酸梯度转移。
Low levels of ADP binding at the ADP/ATP translocase caused inhibition of the Ca2+-induced permeability transition of the mitochondrial inner membrane, when measured using the shrinkage assay on mitochondria, which have already undergone a transition. Inhibition was prevented by carboxyatractyloside, but potentiated by bongkrekic acid, which increased the affinity for inhibition by ADP. This suggests that inhibition was related to the conformation of the translocase. Ca2+ addition was calculated to remove most of the free ADP. Ca2+ added after ADP induced a slow decay of the inhibition, which probably reflected the dissociation of ADP from the translocator. We conclude that the probability of forming a permeability transition pore (PTP) is much greater when the translocase is in the CAT conformation than in the BKA conformation, and, in the absence of CAT and BKA, the translocator is shifted between the BKA and CAT conformations by ADP binding and removal, even in deenergized mitochondria with no nucleotide gradients.