Corbalan J Jose, Frietze Karla K, Nickels Joseph, Sturley Stephen L
Institute of Metabolic Disorders, Genesis Biotechnology Group, 1000 Waterview Drive, Hamilton, NJ 08691, USA.
Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, New Jersey 08901, USA.
Contact (Thousand Oaks). 2025 Jan 17;8:25152564251314601. doi: 10.1177/25152564251314601. eCollection 2025 Jan-Dec.
The composition of eukaryotic membranes reflects a varied but precise amalgam of lipids. The genetic underpinning of how such diversity is achieved or maintained is surprisingly obscure, despite its clear metabolic and pathophysiological impact. The Arv1 protein is represented in all eukaryotes and was initially identified in the model eukaryote as a candidate transporter of lipids from the endoplasmic reticulum. Human Arv1 has been shown to directly bind cholesterol and fatty acid affinity probes. Murine studies point to a role for ARV1 in regulating obesity, glucose tolerance, insulin sensitivity and brain function. Multiple human ARV1 variants have been associated with epileptic encephalopathy, cerebellar ataxia, and severe intellectual deficits. We hypothesize that Arv1 acts as an energy independent, lipid scramblase at the endoplasmic reticulum thereby modulating membrane lipid asymmetry and thus the trafficking of sterols and the substituents of glycosyl-phosphatidylinositol and sphingolipid biosynthesis.
真核细胞膜的组成反映了多种脂质精确融合的结果。尽管这种多样性对代谢和病理生理有明显影响，但其实现或维持的遗传基础却令人惊讶地不清楚。Arv1蛋白存在于所有真核生物中，最初在模式真核生物中被鉴定为内质网脂质的候选转运蛋白。已证明人类Arv1可直接结合胆固醇和脂肪酸亲和探针。小鼠研究表明ARV1在调节肥胖、葡萄糖耐量、胰岛素敏感性和脑功能方面发挥作用。多种人类ARV1变体与癫痫性脑病、小脑共济失调和严重智力缺陷有关。我们假设Arv1在内质网中作为一种能量非依赖性脂质翻转酶发挥作用，从而调节膜脂质不对称性，进而调节固醇的运输以及糖基磷脂酰肌醇和鞘脂生物合成的取代基。
