Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency  

作　　者：Jinglin Zhu Sin Man Lam Leilei Yang Jingjing Liang Mei Ding Guanghou Shui Xun Huang 

机构地区：[1]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Life Metabolism》2022年第2期175-189,共15页生命（代谢（英文）

基　　金：supported by the National Natural Science Foundation of China(9195420001);the Ministry of Science and Technology of China(2018YFA0506902).

摘　　要：Seipin plays a vital role in lipid droplet homeostasis,and its deficiency causes congenital generalized lipodystrophy type II in humans.It is not known whether the physiological defects are all caused by cellular lipid droplet defects.Loss-of-function mutation of seip-1,the Caenorhabditis elegans seipin ortholog,causes embryonic lethality and lipid droplet abnormality.We uncover nhr-114 and spin-4 as two suppressors of seip-1 embryonic lethality.Mechanistically,nhr-114 and spin-4 act in the“B12-one-carbon cycle-phosphatidylcholine(PC)”axis,and reducing PC synthesis suppresses the embryonic lethality of seip-1 mutants.Conversely,PC deficiency enhances the lipid droplet abnormality of seip-1 mutants.The suppression of seip-1 embryonic lethality by PC reduction requires polyunsaturated fatty acid.In addition,the suppression is enhanced by the knockdown of phospholipid scramblase epg-3.Therefore,seipin and PC exhibit opposite actions in embryogenesis,while they function similarly in lipid droplet homeostasis.Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis.

关 键 词：seipin PHOSPHATIDYLCHOLINE EMBRYOGENESIS lipid droplet 

分 类 号：R321[医药卫生—人体解剖和组织胚胎学]