Visser Ankia, Hussain M Mahmood, Kuivenhoven Jan Albert
Department of Pediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA.
Curr Opin Lipidol. 2025 Jun 1;36(3):145-152. doi: 10.1097/MOL.0000000000000983. Epub 2025 Mar 28.
Chylomicron biosynthesis plays a vital role in supplying essential lipids and lipid soluble vitamins to peripheral tissues for various functions. Despite this, the intracellular synthesis, trafficking, and secretion of chylomicrons remains only partly understood. The purpose of this review is to summarize the role of established proteins in this process and bring attention to recently identified proteins to provide an up-to-date model of chylomicron biosynthesis.
Recently, several proteins have been shown to play a role in the initial formation and lipidation of chylomicrons at the endoplasmic reticulum (ER), which include: TM6SF2, PLA2G12B, PRAP1, and SURF4. In addition, mitochondria have been implicated in chylomicron metabolism, but mechanistic insight is missing. The trafficking of chylomicrons from the ER to the Golgi, and the subsequent trafficking from the Golgi to the basolateral side of enterocytes, however, remains a mystery.
Progress in the chylomicron biosynthesis field is largely associated with findings in VLDL biosynthesis. In addition, increased insight in events after prechylomicrons leave the ER is needed. Given the important role of chylomicron biosynthesis in whole-body lipid metabolism, further research into the molecular mechanisms is warranted.
乳糜微粒生物合成在为外周组织提供必需脂质和脂溶性维生素以实现各种功能方面发挥着至关重要的作用。尽管如此，乳糜微粒的细胞内合成、运输和分泌仍仅被部分理解。本综述的目的是总结已确定的蛋白质在这一过程中的作用，并关注最近鉴定出的蛋白质，以提供一个最新的乳糜微粒生物合成模型。
最近，几种蛋白质已被证明在内质网（ER）中乳糜微粒的初始形成和脂化过程中发挥作用，其中包括：跨膜6次蛋白超家族成员2（TM6SF2）、磷脂酶A2G12B（PLA2G12B）、前蛋白转化酶枯草溶菌素9（PRAP1）和转运和加工因子4（SURF4）。此外，线粒体也参与了乳糜微粒的代谢，但缺乏机制上的见解。然而，乳糜微粒从内质网到高尔基体的运输，以及随后从高尔基体到肠细胞基底外侧的运输，仍然是一个谜。
乳糜微粒生物合成领域的进展在很大程度上与极低密度脂蛋白（VLDL）生物合成的研究结果相关。此外，需要对乳糜微粒前体离开内质网后的事件有更多的了解。鉴于乳糜微粒生物合成在全身脂质代谢中的重要作用，有必要进一步研究其分子机制。
