Duramycin effects on the structure and function of heart mitochondria. I. Structural alterations and changes in membrane permeability.
Duramycin effects on the structure and function of heart mitochondria. I. Structural alterations and changes in membrane permeability.
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耐久霉素对心脏线粒体的结构和功能有影响。
DOI：
10.1016/0005-2736(89)90374-x
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Sikora-VanMeter,K
中科院分区：
文献类型：
--
作者：
Sokolove,PM;Westphal,PA;Kester,MB;Wierwille,R;Sikora-VanMeter,K
据报道，多肽抗生素耐久霉素与两种脂质发生特异性相互作用：磷脂酰乙醇胺 (PE) 和单半乳糖基二酰基甘油（Navarro 等人 (1985) Biochemistry 24, 4645–4650）。 PE是线粒体膜的主要成分。使用耐久霉素来检查 PE 在维持线粒体结构和膜通透性特性中的作用，结果如下：(1) 将耐久霉素添加到分离的大鼠心脏线粒体中会产生突然的细胞器收缩，随后根据悬浮介质的组成，出现明显的肿胀。抗生素最显着的形态效应是外膜起皱或锯齿状，最终导致其与内膜分离。 (2)低浓度(<5μM)的抗生素选择性地增加线粒体内膜对阳离子和小溶质的通透性。这种效应被白术苷（腺嘌呤核苷酸易位蛋白的高度特异性抑制剂）、棕榈酰辅酶 A、N-乙基马来酰亚胺以及 AMP、ADP 和 ATP 阻断，但不被 GDP 或 GTP 阻断，这表明腺嘌呤核苷酸易位蛋白在选择性通透性增加中起作用。 (3)较高浓度的耐久霉素诱导更普遍的通透性增加，该增加不受能够与腺嘌呤核苷酸易位子相互作用的化合物的抑制。
The polypeptide antibiotic duramycin has been reported to interact specifically with two lipids: phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (Navarro et al. (1985) Biochemistry 24, 4645–4650). PE is a major component of mitochondrial membranes. Duramycin was used to examine the role of PE in maintenance of mitochondrial structure and membrane permeability properties with the following results: (1) Duramycin addition to isolated rat heart mitochondria produced abrupt organelle contraction which was followed, depending on composition of the suspending medium, by pronounced swelling. The most notable morphological effect of the antibiotic was ruffling or crenelation of the outer membrane, which resulted ultimately in its separation from the inner membrane. (2) Low concentrations (< 5 μM) of the antibiotic selectively increased the permeability of the mitochondrial inner membrane to cations and small solutes. This effect was blocked by atractyloside, a highly specific inhibitor of the adenine nucleotide translocator, by palmitoyl coenzyme A, byN-ethylmaleimide, and by AMP, ADP and ATP but not GDP or GTP, implicating the adenine nucleotide translocator in the selective permeability increase. (3) Higher concentrations of duramycin induced a more generalized permeability increase which was no subject to inhibition by compounds capable of interacting with the adenine nucleotide translocator.