FUNCTION OF CARDIOLIPIN PHASE POLYMORPHISM

生物膜的基本功能是在 细胞隔间。对于线粒体膜内层，低 对质子的渗透性似乎特别重要，因为质子 跨膜的梯度驱动线粒体中ATP的合成。 用脂泡直接测量质子的渗透性 吡喃，一种荧光pH指示剂，已经被捕获，并分析了 数字化速率提供3-4 x 10-3厘米/秒的值，更大的值 渗透率，因为质子浓度很低 生理PH值，以及可能的特殊策略，实际被动 体内的线粒体质子通量必须与 电子传输系统的适当质子泵浦速率。 心磷脂或二磷脂酰甘油是一种唯一定位的磷脂 几乎只对线粒体起作用。这种分子表现出很强的 细胞色素c等固有膜蛋白表面亲和力的研究 用自旋标记的心磷脂类似物和31P-核磁共振显示了氧化酶。 这种脂类还表现出相多态，用31P- 核磁共振和低角X射线衍射，从片层相转变为 当盐浓度提高到1.5m以上时，出现倒六方相。 这一阶段的多态已经被证明，使用心磷脂类似物 不同数量的脂肪酰链，是形状的函数 分子。虽然越来越多的证据排除了形成非 体内的片层相，这种分子的形状，以及它的 对固有膜蛋白的异常亲和力，指向一种独特的 心磷脂对这些系统的不规则表面的封闭作用 由二磷脂酰胆碱和细胞色素氧化酶组成的蛋白质脂质体 使用和不使用心磷脂。两种材料质子渗透率的比较 这两种类型的水泡应该提供支持或反对的证据 假设心磷脂防止质子或其他离子通过 双层和蛋白质表面之间的界面。 在心脏组织中，溶血磷脂和游离脂肪酸在 心肌梗死可能增加心肌细胞的质子通透性 线粒体，解偶联电子传递，限制ATP合成， 直接导致细胞死亡。这一分子基础的论证 细胞死亡将使患者能够更好地干预和治疗 心脏病。

A basic function of a biological membrane is to provide a barrier between cellular compartments. For the inner mitochondrial membrane, low permeability to protons seems particularly crucial because the proton gradient across this membrane drives the synthesis of ATP in mitochondria. Direct measurement of the proton permeability using lipid vesicles in which pyranine, a fluorescent pH indicator, has been trapped, and analysis of the digitized rates provides values of 3-4 x 10-3 cm/sec, much larger values that the permeability, because of the low concentration of protons at physiological pH, and possible special strategies, the actual passive mitochondrial proton flux in vivo must be more than adequately matched by adequate proton pumping rates by the electron transport system. Cardiolipin or diphosphatidylglycerol is a unique phospholipid localized almost exclusively to the mitochondrion. The molecular exhibits a strong affinity for the surface of intrinsic membrane proteins like cytochrome c oxidase is shown using spin-labeled cardiolipin analogues and 31P-NMR. This lipid also exhibits phase polymorphism, as measured in bulk using 31P- NMR and low angle X-ray diffraction, converting from lamellar phase to the inverted hexagonal phase when the salt concentration is raised above 1.5M. This phase polymorphism has been shown, using cardiolipin analogues with differing numbers of fatty acyl chains, to be a function of the shape of the molecule. While increasing evidence rules out the formation of non- lamellar phases in vivo, the shape of this molecule, together with its unusual affinity for intrinsic membrane proteins, points toward a unique function for cardiolipin sealing the irregular surface of these system of proteoliposomes composed of diphosphatidylcholine and cytochrome oxidase with and without cardiolipin. Comparison of the proton permeabilities of these two types of vesicles should provide evidence for or against the hypothesis that cardiolipin prevent proton or other ion leaks through the interface between the bilayer and the protein surface. In heart tissue, lysophospholipids and free fatty acids formed during myocardial infarct probably increase the proton permeability of mitochondria, uncoupling electron transport, and limiting ATP synthesis, directly resulting in cell death. Demonstration of this molecular basis of cell death would enable better intervention and treatment of patients with heart disease.