Redox Biology:中科院遗传所税光厚研究组揭示膜脂平衡影响秀丽线

2017年5月4日，国际杂志《Redox BioLogy》在线发表了中国科学院遗传与发育生物学研究所税光厚研究组的一篇研究论文，论文报道了膜脂平衡影响秀丽线虫持久幼虫寿命的新机制。税光厚研究组的Lam Sin Man博士、博士研究生王泽华和博士研究生李婕是该文的共同第一作者，税光厚研究员为该论文的通讯作者。

在秀丽隐杆线虫中存在一种不衰老的发育模式，其主要表现为持久幼虫停止发育并尽可能的延长存活时间，但是其具体的调控机制目前还不清楚。

研究组从脂质组学分析和相关基因转录水平调控入手，分析了持久幼虫衰老和死亡过程中膜脂上特定的脂酰基团的转变，发现与线虫的其他发育时期相比，进入耐受态的持久幼虫的膜磷脂上会富集多不饱和脂肪酸。进一步研究发现，持久幼虫的膜磷脂中的多聚不饱和脂肪酸含量在维持幼虫耐受态的前半程逐渐累积。而当持久幼虫开始死亡时，膜脂中的多不饱和脂肪酸骤然减少，游离态的多不饱和脂肪酸及其下游的氧化衍生物大量增加。脂质组学分析显示多聚不饱和脂肪酸富集在磷脂膜上，对耐受态线虫的休眠具有不可或缺的作用，其主要的作用是抑制下游产物类花生酸类物质的形成，并且打破膜脂平衡会促使持久幼虫死亡或退出耐受态。研究揭示了膜脂中不饱和脂肪酸的变化可能是影响长寿的重要因素之一。

Sequestration of polyunsaturated fatty acids in membrane phospholipids of Caenorhabditis elegans dauer larva attenuates eicosanoid biosynthesis for prolonged survival

原文摘要：

Mechanistic basis governing the extreme longevity and developmental quiescence of dauer juvenile, a “non-ageing” developmental variant of Caenorhabditis elegans, has remained largely obscure. Using a lipidomic approach comprising multiple reaction monitoring transitions specific to distinct fatty acyl moieties, we demonstrated that in comparison to other developmental stages, the membrane phospholipids of dauer larva contain a unique enrichment of polyunsaturated fatty acids (PUFAs). Esterified PUFAs in phospholipids exhibited temporal accumulation throughout the course of dauer endurance, followed by sharp reductions prior to termination of diapause. Reductions in esterified PUFAs were accompanied by concomitant increases in unbound PUFAs, as well as their corresponding downstream oxidized derivatives (i.e. eicosanoids). global phospholipidomics has unveiled that PUFA sequestration in membrane phospholipids denotes an essential aspect of dauer dormancy, principally via suppression of eicosanoid production; and a failure to upkeep membrane lipid homeostasis is associated with termination of dauer endurance.

doi:10.1016/j.redox.2017.05.002

作者：税光厚