MITOCHONDRIAL MEMBRANE METABOLIC ROLE OF CYTOCHROME C

细胞色素 C 的线粒体膜代谢作用

• 批准号: 3269522
• 负责人: EMANUEL MARGOLIASH
• 金额: $ 32.63万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269522
• 关键词: analytical method; biological information processing; cellular respiration; chemical synthesis; crosslink; cytochrome b; cytochrome b2; cytochrome c; cytochrome oxidase; electron transport; enzyme structure; immunochemistry; ionic strengths; isozymes; mathematical model; membrane activity; membrane potentials; membrane structure; mitochondrial membrane; oxidative phosphorylation; oxidoreductase; phospholipids; radiotracer; species difference; succinate dehydrogenase; yeasts

Cytochrome c is the only protein component of th mitochondrial respiratory chain that is not an integral protein of the inner mitochondrial membrane, but rather can readily dissociate from the outer surface of the membrane into the intermembrane space. Even though a wealth of information is available concerning many aspects of its operation there still exists a fundamental lack of knowledge about the mechanics of its function under normal intracellular physiological conditions. Thus, the transfer of electrons between the reductase and oxidase segments of the repsiratory chain, the major but not the only function of cytochrom c, could take place with very little movement of the protein (solid state model) by two-dimensional diffusion along the outer surface of the inner mitochondiral membrane or by free diffusion in the intermembrane space. Which of these processes or combinations of processes occurs, will depend on ionic strength, ionic composition, the appropriate Donnan equiibria, the large electric field generated by fixed charges on the membrane (estimated at 18.4x106 volt/meter), the occurrence of oxidative phosphoration and the morphological changes of the mitochondrial inner membrane attending changes in state of activity. There forces may be geared to operating cytochrome c as an on-off switch effecting respiratory control. To describe its physiological function it is proposed to: (1) develop biosynthetic procedures for inserting cytochrome c carrying a variety of labels into strictly intact mitochondria and use such preparations to define intramitochondrial localization and mobility of cytochrome c under functional conditions; (2) study the covalent crosslinking of cytochrome c to artificial membranes, isolated enzyme systems and mitochondrial inner membranes, as controls to the concepts developed under Section 1, and examine the role of phospholipid in cytochrome c binding; (3) examine the kinetic control of succinate oxidase activity by cytochrome c in mirochondiral inner membrane preparations; (4) continue chemical modification studies to examine the electron transfer reactions with cytochrome c peroxidase and the b5 superfamily of electron transfer proteins. These and related studies are expected to define the precise mode of physiological regulation of cytochrome c, leading the way to possible approaches to its artificial control.

细胞色素c是线粒体呼吸系统中唯一的蛋白质成分。 不是线粒体内膜的完整蛋白质的链， 而是可以容易地从膜的外表面解离 进入膜间隙 尽管大量的信息 关于其运作的许多方面，仍然存在一个 基本上缺乏关于其功能机制的知识， 正常的细胞内生理条件。 因此， 还原酶和氧化酶片段之间的电子 细胞色素c的主要功能，但不是唯一的功能， 蛋白质的运动非常小（固态模型）， 沿着内表面的外表面的二维扩散 线粒体膜或通过膜间隙中的自由扩散。 这些过程中的哪一个或过程的组合发生，将取决于 离子强度、离子组成、适宜的道南平衡、 膜上固定电荷产生的大电场（估计 在18.4x106伏/米），氧化磷化的发生和 线粒体内膜的形态学变化 处于活动状态。 这些力量可能是为了操纵细胞色素c 作为影响呼吸控制的开关。 来描述其 生理功能，建议：（1）开发生物合成 将携带多种标记的细胞色素c插入到 严格完整的线粒体，并使用这种制剂来定义 细胞色素c在线粒体内定位和迁移率 功能条件;（2）研究细胞色素c的共价交联 人工膜，分离的酶系统和线粒体内 膜，作为第1节中开发的概念的控制，以及 检查磷脂在细胞色素c结合中的作用;（3）检查 细胞色素c对琥珀酸氧化酶活性动力学调控 微软骨内膜制备;（4）继续化学 改性研究，以检查电子转移反应， 细胞色素c过氧化物酶与电子传递b5超家族 proteins. 这些和相关的研究预计将确定精确的 细胞色素c的生理调节模式， 人为控制的可能方法。