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Regulation of the protein disulfide proteome by mitochondria in mammalian cells

机译:线粒体对哺乳动物细胞中蛋白质二硫键蛋白质组的调控

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The majority of protein disulfides in cells is considered an important inert structural, rather than a dynamic regulatory, determinant of protein function. Here, we show that some disulfides in proteins also are regulated by cell redox status with functional consequences. We find that reactive oxygen species (ROS) produced by mitochondria are actively used by cells to facilitate cell-surface protein disulfide formation, as well as folding and transport, in mammalian cells. Inhibition of mitochondria) ROS production suppresses protein disulfide formation and induces reductive stress, leading to dysfunction and retention (possibly in the Golgi, in part) of a group of cell-surface disulfide-containing proteins. Sparsely cultured cells produce less ROS than confluent cells do, which leads to decreased disulfide formation and decreased activity of a subgroup of disulfide-containing cell-surface receptors. These data support the concept of two subproteomes comprising the disulfide proteome, a structural group and a redox-sensitive regulatory group, with the latter having direct functional consequences for the cell.
机译:细胞中大多数蛋白质二硫键被认为是蛋白质功能的重要惰性结构,而非动态调节因素。在这里,我们显示蛋白质中的某些二硫化物也受到细胞氧化还原状态的调节,并具有功能性后果。我们发现,线粒体产生的活性氧(ROS)被细胞积极地用于促进哺乳动物细胞中细胞表面蛋白质二硫键的形成以及折叠和运输。抑制线粒体ROS的产生会抑制蛋白质二硫键的形成并诱导还原性应激,从而导致一组细胞表面含二硫键的蛋白质功能失调和滞留(可能在高尔基体中部分存在)。稀疏培养的细胞产生的ROS低于融合细胞,产生的ROS减少,导致二硫键的形成减少,含二硫键的细胞表面受体亚组的活性降低。这些数据支持包括二硫键蛋白质组,结构基团和氧化还原敏感的调节基团的两个子蛋白质组的概念,后者对细胞具有直接的功能影响。

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