Lipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein - expressed in retina, brain, Meibomian glands, skin, testes and sperm - is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles in maintaining retina and brain function, neuroprotection, skin permeability barrier maintenance and sperm function, among other important cellular processes. Mutations in ELOVL4 that affect biosynthesis of these fatty acids cause several distinct tissue-specific human disorders that include blindness, age-related cerebellar atrophy and ataxia, skin disorders, early-childhood seizures, mental retardation and mortality, which underscores the essential roles of ELOVL4 products for life. However, the mechanisms by which one tissue makes VLC-PUFA and another makes VLC-SFA, and how these fatty acids exert their important functional roles in each tissue, remain unknown. This review summarizes research over that last decade that has contributed to our current understanding of the role of ELOVL4 and its products in cellular function. In the retina, VLC-PUFA and their bioactive "Elovanoids" are essential for retina function. In the brain, VLC-SFA are enriched in synaptic vesicles and mediate neuronal signaling by determining the rate of neurotransmitter release essential for normal neuronal function. These findings point to the ELOVL4 and its products as being essential for life. Therefore mutations and or age-related epigenetic modifications of fatty acid biosynthetic gene activity that affect VLC-SFA and VLC-PUFA biosynthesis contribute to age-related dysfunction of ELOVL4 expressing tissues.

中文翻译：

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含极长链脂肪酸的脂质：ELOVL4 研究十年来的新见解。


脂质通过调节膜流动性和细胞信号传导在维持细胞结构和功能方面发挥重要作用。脂肪酸延长酶 4 (ELOVL4) 蛋白在视网膜、大脑、睑板腺、皮肤、睾丸和精子中表达，是介导 VLC-PUFA 和 VLC 饱和脂肪酸 (VLC-国家安全局）。这些脂肪酸在维持视网膜和大脑功能、神经保护、皮肤渗透屏障维护和精子功能以及其他重要的细胞过程中发挥着关键作用。 ELOVL4 中影响这些脂肪酸生物合成的突变会导致几种不同的组织特异性人类疾病，包括失明、年龄相关的小脑萎缩和共济失调、皮肤病、儿童早期癫痫发作、智力低下和死亡，这强调了 ELOVL4 的重要作用终生产品。然而，一种组织产生 VLC-PUFA 和另一种组织产生 VLC-SFA 的机制，以及这些脂肪酸如何在每种组织中发挥其重要的功能作用，仍然未知。这篇综述总结了过去十年的研究，这些研究有助于我们目前了解 ELOVL4 及其产物在细胞功能中的作用。在视网膜中，VLC-PUFA 及其生物活性“Elovanoids”对于视网膜功能至关重要。在大脑中，VLC-SFA 富含突触小泡，并通过确定正常神经元功能所必需的神经递质释放速率来介导神经元信号传导。这些发现表明 ELOVL4 及其产品对生命至关重要。 因此，影响VLC-SFA和VLC-PUFA生物合成的脂肪酸生物合成基因活性的突变和/或年龄相关的表观遗传修饰导致ELOVL4表达组织的年龄相关功能障碍。