INVOLVEMENT OF THE ADP/ATP CARRIER IN CALCIUM-INDUCED PERTURBATIONS OF THE MITOCHONDRIAL INNER MEMBRANE-PERMEABILITY - IMPORTANCE OF THE ORIENTATION OF THE NUCLEOTIDE BINDING-SITE
INVOLVEMENT OF THE ADP/ATP CARRIER IN CALCIUM-INDUCED PERTURBATIONS OF THE MITOCHONDRIAL INNER MEMBRANE-PERMEABILITY - IMPORTANCE OF THE ORIENTATION OF THE NUCLEOTIDE BINDING-SITE
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DOI：
10.1016/0003-9861(88)90125-7
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发表时间：
1988-09-01
影响因子：
3.9
通讯作者：
LEQUOC, D
中科院分区：
文献类型：
--
作者：
LEQUOC, K;LEQUOC, D
从含钙线粒体中诱导钙外排的化合物通常会引起膜渗漏。研究了ADP - ATP载体在线粒体膜性质修饰中的作用。在装载钙的线粒体中添加不当的ADP ATP载体抑制剂，即羧酸atractylate、棕榈酰基辅酶A（在没有肉碱的情况下）和吡哆醛5-磷酸，会引发积累的钙的释放、内源性ADP的泄漏和线粒体的肿胀。渗透配体，如bongkrek酸或ADP，对膜通透性无损伤作用；事实上，它们阻碍了由三种非本意效应物引起的膜扰动。此外，bongkrekic酸和ADP都能抵消乙酰乙酸氧化线粒体内吡啶核苷酸引起的钙损失和肿胀。在醋酸酯处理的线粒体中，ADP ATP载体主要呈c态构象（即核苷酸结合位点具有外取向）。结果表明，钙离子诱导细胞膜渗漏取决于腺嘌呤核苷酸载体的构象状态。线粒体内钙离子修饰膜性质的能力是由核苷酸结合位点的取向决定的。只有c态构象允许膜不稳定。因此，所有将ADP ATP载体稳定在c态构象的化合物都会对含钙线粒体产生有害影响。
Compounds which induce calcium efflux from calcium-loaded mitochondria generally provoke membrane leakiness. The involvement of the ADP ATP carrier in modification of mitochondrial membrane properties was studied. The addition of impermeant inhibitors of the ADP ATP carrier, namely carboxyatractylate, palmitoyl coenzyme A (in the absence of carnitine), and pyridoxal 5-phosphate, to calcium-loaded mitochondria triggered the release of accumulated calcium, the leakage of endogenous ADP, and the swelling of mitochondria. Permeant ligands, such as bongkrekic acid or ADP, showed no damaging effect on membrane permeability; in fact, they impeded the membrane perturbation which was induced by the three impermeant effectors. In addition, both bongkrekic acid and ADP were able to cancel the calcium loss and swelling resulting from the oxidation of intramitochondrial pyridine nucleotides by acetoacetate. In acetoacetate-treated mitochondria, the ADP ATP carrier was shown to be mainly in a c-state conformation (ie, the nucleotide binding site had an external orientation). It was concluded that induction of membrane leakiness by calcium ions depends on the conformational state of the adenine nucleotide carrier. The ability of intramitochondrial calcium ions to modify membrane properties is determined by the orientation of the nucleotide binding site. Only the c-state conformation allows membrane destabilization. Consequently, all compounds which stabilize the ADP ATP carrier in the c-state conformation will have a deleterious effect on calcium-loaded mitochondria.