THE MECHANISM OF THE INCREASE IN MITOCHONDRIAL PROTON PERMEABILITY INDUCED BY THYROID-HORMONES
THE MECHANISM OF THE INCREASE IN MITOCHONDRIAL PROTON PERMEABILITY INDUCED BY THYROID-HORMONES
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DOI：
10.1111/j.1432-1033.1992.tb16984.x
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发表时间：
1992-06-15
期刊：
影响因子：
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通讯作者：
HAFNER, RP
中科院分区：
文献类型：
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作者：
BRAND, MD;STEVERDING, D;HAFNER, RP
研究了三种可能的机制，大鼠体内不同水平的甲状腺激素可能导致分离的肝线粒体内膜的表观质子渗透性发生七倍的变化。 (a) 从甲状腺功能减退、甲状腺功能正常和甲状腺功能亢进大鼠的肝脏中分离出细胞色素 c 氧化酶，并将其掺入由大豆磷脂制成的脂质体中。三种囊泡的质子电流/电压曲线没有差异。因此，激素效应不是酶的固有特性，也不是由于通过酶的电子流与质子传输的不同耦合所致。 (b) 三种不同的测定表明，甲状腺功能亢进动物的线粒体的线粒体内膜表面积比甲状腺功能减退动物的线粒体大二至三倍；甲状腺功能正常对照处于中等水平。内膜表面积的差异解释了表观质子渗透性差异的不到一半。 (c)用从甲状腺功能亢进大鼠线粒体内膜提取的磷脂制备的脂质体的质子渗透性是甲状腺功能减退大鼠的质子渗透性的三倍；甲状腺功能正常对照处于中等水平。这表明，首先，磷脂双层的质子渗透性是完整线粒体中质子渗透性的重要组成部分，其次，甲状腺激素诱导的双层变化是质子渗透性增加机制的主要部分。这种变化可能是由于已知不同甲状腺状态下线粒体磷脂的脂肪酸组成存在差异。因此，我们确定了大鼠甲状腺激素水平改变离体肝线粒体中质子通量/质量蛋白的两种机制：内膜/质量蛋白面积的变化和磷脂双层内在渗透性的变化。
Three possible mechanisms by which different levels of thyroid hormones in rats might cause the observed sevenfold change in the apparent proton permeability of the inner membrane of isolated liver mitochondria were investigated. (a) Cytochrome c oxidase was isolated from the livers of hypothyroid, euthyroid and hyperthyroid rats and incorporated into liposomes made with soya phospholipids. There was no difference between the proton current/voltage curves of the three types of vesicles. The hormonal effects, therefore, were not an inherent property of the enzymes, and were not due to different coupling of electron flow through the enzyme to proton transport. (b) The surface area of the mitochondrial inner membrane was shown by three different assays to be greater by a factor of between two and three in mitochondria from hyperthyroid animals than in mitochondria from hypothyroid animals; euthyroid controls were intermediate. This difference in surface area of the inner membrane explains less than half of the difference in apparent proton permeability. (c) The proton permeability of liposomes prepared from phospholipids extracted from mitochondrial inner membranes of hyperthyroid rats was three times greater than the proton permeability of those from hypothyroid rats; euthyroid controls were intermediate. This suggests, first, that the proton permeability of the phospholipid bilayer is an important component of the proton permeability in intact mitochondria and, second, thyroid hormone-induced changes in the bilayer are a major part of the mechanism of increased proton permeability. Such changes may be due to the known differences in fatty acid composition of mitochondrial phospholipids in different thyroid states. Thus we have identified two mechanisms by which thyroid hormone levels in rats change proton flux/mass protein in isolated liver mitochondria: a change in the area of the inner membrane/mass protein and a change in the intrinsic permeability of the phospholipid bilayer.