Regulation of plasmalogen synthesis and establishment of plasmalogen diversity

本研究旨在探讨纤溶酶原合成调控的分子机制。血浆蛋白原是甘油磷脂的一种亚型，其中长链脂肪醇通过乙烯基醚键在sn-1位连接。过氧异构体脂肪酰辅酶A还原酶1(FAR1)是血浆原合成中醚键形成所必需的脂肪醇的供给者。纤溶酶原的合成是通过调节Far1的稳定性来调节的，这是一种依赖于纤溶酶原的方式。在这里，我发现Far1是一个过氧化物体尾部锚定蛋白。FAR1，而不是FAR2，优先被胞内水平的血浆原降解。Far1跨膜区两侧的区域是依赖于纤溶酶原的Far1降解所必需的。血浆蛋白原的多样性是通过脂肪酸的重塑形成的，而FAR1的稳定性取决于某些类型的血浆蛋白原。

The aim of this study is to investigate molecular mechanism of the regulation of plasmalogen synthesis. Plasmalogen is a subtype of glycerophospholipids, in which a long chain fatty alcohol is linked at sn-1 position through a vinyl ether bond. Peroxisomal fatty acyl-CoA reductase 1 (Far1) is essential for supplying fatty alcohols required for ether bond formation in plasmalogen synthesis. Plasmalogen synthesis is regulated by modulating Far1 stability in a plasmalogen-dependent manner.Here I found that Far1 is a peroxisomal tail-anchored protein. Far1, but not Far2, was preferentially degraded in response to the cellular level of plasmalogens. The region flanking the transmembrane domain of Far1 is required for plasmalogen-dependent degradation of Far1. The diversity of plasmalogens was formed through remodeling of fatty acids and Far1 stability is regulated in a manner dependent on certain type of plasmalogens.