Jinglin Zhu, S. Lam, Lei-lei Yang, Jingjing Liang, Mei Ding, G. Shui, Xun Huang
{"title":"磷脂酰胆碱合成减少可抑制赛品缺乏症的胚胎致死率","authors":"Jinglin Zhu, S. Lam, Lei-lei Yang, Jingjing Liang, Mei Ding, G. Shui, Xun Huang","doi":"10.1093/lifemeta/loac021","DOIUrl":null,"url":null,"abstract":"\n 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 C. 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 (PUFA). In addition, the suppression is enhanced by knockdown of phospholipid scramblase epg-3. Therefore, seipin and phosphatidylcholine 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.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency\",\"authors\":\"Jinglin Zhu, S. Lam, Lei-lei Yang, Jingjing Liang, Mei Ding, G. Shui, Xun Huang\",\"doi\":\"10.1093/lifemeta/loac021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n 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 C. 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 (PUFA). In addition, the suppression is enhanced by knockdown of phospholipid scramblase epg-3. Therefore, seipin and phosphatidylcholine 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.\",\"PeriodicalId\":74074,\"journal\":{\"name\":\"Life metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life metabolism\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/lifemeta/loac021\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/lifemeta/loac021","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency
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 C. 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 (PUFA). In addition, the suppression is enhanced by knockdown of phospholipid scramblase epg-3. Therefore, seipin and phosphatidylcholine 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.