Nunes Lance G A, Ma Chi, Pitts Matthew W, Hoffmann Peter R
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA.
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA.
Arch Biochem Biophys. 2025 Jun;768:110394. doi: 10.1016/j.abb.2025.110394. Epub 2025 Mar 17.
Selenoprotein I (selenoi) is a metabolic enzyme expressed in a wide variety of tissues that catalyzes the transfer of the ethanolamine phosphate group from CDP-ethanolamine to lipid acceptors to generate ethanolamine phospholipids. It is a member of the selenoprotein family, a class of proteins that mostly play fundamental roles in redox homeostasis and are defined by the co-translational incorporation of selenium in the form of selenocysteine. Loss-of-function mutations in the human SELENOI gene have been found in rare cases leading to a complex form of hereditary spastic paraplegia. Understanding the roles of this selenoprotein and its phospholipid products in different cell types has benefited from the development of mouse models. In particular, global and conditional knockout (KO) of the Selenoi gene in mice has enabled a more complete picture to emerge of how this important selenoprotein is integrated into metabolic pathways. These data have revealed how Selenoi loss-of-function affects embryogenesis, neurodevelopment, the immune system and liver physiology. This review summarizes the insights gained through mouse model experiments and the current understanding the different physiological roles played by this selenoprotein.
硒蛋白I（selenoi）是一种在多种组织中表达的代谢酶，它催化磷酸乙醇胺基团从胞苷二磷酸乙醇胺转移到脂质受体上，以生成乙醇胺磷脂。它是硒蛋白家族的一员，这类蛋白质大多在氧化还原稳态中发挥重要作用，并通过共翻译将硒以硒代半胱氨酸的形式掺入而得以定义。在罕见病例中发现人类SELENOI基因的功能丧失突变会导致一种复杂形式的遗传性痉挛性截瘫。小鼠模型的发展有助于了解这种硒蛋白及其磷脂产物在不同细胞类型中的作用。特别是，在小鼠中对Selenoi基因进行全身性和条件性敲除（KO），使人们能够更全面地了解这种重要的硒蛋白是如何整合到代谢途径中的。这些数据揭示了Selenoi功能丧失如何影响胚胎发生、神经发育、免疫系统和肝脏生理。本综述总结了通过小鼠模型实验获得的见解以及目前对这种硒蛋白所发挥的不同生理作用的理解。
