Institute of Molecular, Cellular and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Trends Biochem Sci. 2011 Sep;36(9):485-92. doi: 10.1016/j.tibs.2011.05.004. Epub 2011 Jul 19.
Our concept of how disulfides form in proteins entering the secretory pathway has changed dramatically in recent years. The discovery of endoplasmic reticulum (ER) oxidoreductin 1 (ERO1) was followed by the demonstration that this enzyme couples oxygen reduction to de novo formation of disulfides. However, mammals deficient in ERO1 survive and form disulfides, which suggests the presence of alternative pathways. It has recently been shown that peroxiredoxin 4 is involved in peroxide removal and disulfide formation. Other less well-characterized pathways involving quiescin sulfhydryl oxidase, ER-localized protein disulfide isomerase peroxidases and vitamin K epoxide reductase might all contribute to disulfide formation. Here we discuss these various pathways for disulfide formation in the mammalian ER and highlight the central role played by glutathione in regulating this process.
近年来，我们对蛋白质进入分泌途径时二硫键形成方式的认识发生了巨大变化。内质网（ER）氧化还原酶 1（ERO1）的发现，随后证明该酶将氧还原与新形成的二硫键偶联。然而，缺乏 ERO1 的哺乳动物能够存活并形成二硫键，这表明存在替代途径。最近的研究表明，过氧化物酶 4 参与过氧化物的清除和二硫键的形成。其他不太为人所知的途径，包括静止硫氧还蛋白、内质网定位的蛋白二硫键异构酶过氧化物酶和维生素 K 环氧化物还原酶，都可能参与二硫键的形成。在这里，我们讨论了哺乳动物 ER 中这些不同的二硫键形成途径，并强调了谷胱甘肽在调节这一过程中的核心作用。
