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bioRxiv · 10.1101/2022.04.10.487805

Contrasting effects of reduced phosphatidylcholine synthesis in absence of seipin: embryonic lethality goes down while lipid droplets get even larger

Zhu, J.·Lam, S. M.·Yang, L.·Liang, J.·Ding, M.·Shui, G.·Huang, X.
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Abstract

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). 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. HighlightsO_LIseip-1 suppressors act in the "B12-one-carbon cycle-PC" pathway. C_LIO_LIReducing PC synthesis suppresses the embryonic lethality of seip-1 mutants. C_LIO_LISuppression of the embryonic lethality by PC reduction requires PUFA. C_LIO_LIReduced PC synthesis enhances the large lipid droplet of seip-1 mutants. C_LI

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Zhu, J., Lam, S. M., Yang, L., Liang, J., Ding, M., Shui, G., Huang, X.. 2022-04-11. Contrasting effects of reduced phosphatidylcholine synthesis in absence of seipin: embryonic lethality goes down while lipid droplets get even larger. https://doi.org/10.1101/2022.04.10.487805

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