Department of Structural and Molecular Biology, University College London, London, WC1E 6BT, United Kingdom.
Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, United Kingdom.
Biochem Biophys Res Commun. 2019 Apr 2;511(2):294-299. doi: 10.1016/j.bbrc.2019.02.031. Epub 2019 Feb 21.
Dictyostelium discoideum (D. discoideum) is a simple eukaryote with a unique life cycle in which it differentiates from unicellular amoebae into a fruiting body upon starvation. Reactive oxygen species (ROS) have been associated with bacterial predation, as well as regulatory events during D. discoideum development and differentiation. Coenzyme A (CoA) is a key metabolic integrator in all living cells. A novel function of CoA in redox regulation, mediated by covalent attachment of CoA to cellular proteins in response to oxidative or metabolic stress, has been recently discovered and termed protein CoAlation. In this study, we report that the level of CoA and protein CoAlation in D. discoideum are developmentally regulated, and correlate with the temporal expression pattern of genes implicated in CoA biosynthesis during morphogenesis. Furthermore, treatment of growing D. discoideum cells with oxidising agents results in a dose-dependent increase of protein CoAlation. However, much higher concentrations were required when compared to mammalian cells and bacteria. Increased resistance of D. discoideum to oxidative stress induced by HO has previously been attributed to high levels of catalase activity. In support of this notion, we found that HO-induced protein CoAlation is significantly increased in CatA-deficient D. discoideum cells. Collectively, this study provides insights into the role of CoA and protein CoAlation in the maintenance of redox homeostasis in amoeba and during D. discoideum morphogenesis.
集胞藻（D. discoideum）是一种简单的真核生物，其独特的生命周期使其在饥饿时从单细胞变形虫分化为子实体。活性氧（ROS）与细菌捕食以及集胞藻发育和分化过程中的调节事件有关。辅酶 A（CoA）是所有活细胞中的关键代谢整合因子。最近发现了 CoA 的一种新的氧化还原调节功能，即通过 CoA 与细胞蛋白的共价结合来调节氧化或代谢应激，这一功能被称为蛋白 CoAlation。在这项研究中，我们报告了集胞藻中的 CoA 水平和蛋白 CoAlation 受到发育调控，并与形态发生过程中涉及 CoA 生物合成的基因的时间表达模式相关。此外，用氧化剂处理生长中的集胞藻细胞会导致蛋白 CoAlation 剂量依赖性增加。然而，与哺乳动物细胞和细菌相比，需要更高的浓度。先前已经将集胞藻对 HO 诱导的氧化应激的高抵抗力归因于高过氧化氢酶活性。支持这一观点，我们发现 HO 诱导的蛋白 CoAlation 在 CatA 缺陷型集胞藻细胞中显著增加。总的来说，这项研究提供了关于 CoA 和蛋白 CoAlation 在维持变形虫和集胞藻形态发生过程中的氧化还原平衡中的作用的见解。
