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论文名称：
The conserved NUS-1/DHDDS-1 complex links N-glycosylation to lipid and lysosomal homeostasis in C. elegans
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发表刊物：
Cell Reports
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关键字：
N-glycosylation
cis-prenyltransferase complex
lipid homeostasis
lysosomal homeostasis
NUS-1/DHDDS-1
Caenorhabditis elegans
ER stress
SREBP
Research topic(s)
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摘要：
N-glycosylation is essential for proteome integrity, yet the systemic roles of the cis-prenyltransferase (cis-PT) complex remain poorly defined. Using Caenorhabditis elegans, we demonstrate that this complex is a dual regulator of global lipid and lysosomal homeostasis. Mechanistically, NUS-1 physically associates with the core oligosaccharyltransferase (OST) complex to coordinate N-glycan transfer. Loss of NUS-1/DHDDS-1 triggers endoplasmic reticulum stress, lysosomal collapse, and systemic lipopenia. This lipid defect arises from impaired N-glycosylation of the SREBP cleavage-activating protein (SCAP). cis-PT deficiency causes unglycosylated SCAP to undergo massive degradation and absolute physical entrapment within the ER, preventing SREBP nuclear translocation and downstream lipid synthesis. Furthermore, pathogenic mutations cause dysfunction through distinct molecular mechanisms: pocket integrity disruption or catalytic impairment. These findings uncover an essential crosstalk between protein glycosylation and global lipid metabolism, providing a mechanistic framework for understanding the systemic pathophysiology of congenital disorders of glycosylation (CDG).
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第一作者：
Meixi Gong
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通讯作者：
Yilin Du,Wenfei Li,Pei Zhao,张哲
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全部作者：
Wentao Zhao,Lingfan Zhu,Yile Zhai,Yuxiao Xie,Chen Liu
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卷号：
45
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期号：
11
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DOI码：
10.1016/j.celrep.2026.118178
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是否译文：
否
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收录刊物：
SCI
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发布期刊链接：
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发布时间：
2026-11-05
En
