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- W4366993029 endingPage "1071.e12" @default.
- W4366993029 startingPage "1057" @default.
- W4366993029 abstract "Genome-wide association studies (GWASs) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis that associates serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells strongly impairs choline metabolism due to the inhibition of choline import. Consistently, CRISPR-based genetic screens identified phospholipid synthesis and salvage machinery as synthetic lethal with FLVCR1 loss. Cells and mice lacking FLVCR1 exhibit structural defects in mitochondria and upregulate integrated stress response (ISR) through heme-regulated inhibitor (HRI) kinase. Finally, Flvcr1 knockout mice are embryonic lethal, which is partially rescued by choline supplementation. Altogether, our findings propose FLVCR1 as a major choline transporter in mammals and provide a platform to discover substrates for unknown metabolite transporters." @default.
- W4366993029 created "2023-04-27" @default.
- W4366993029 creator A5004696326 @default.
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- W4366993029 creator A5069595952 @default.
- W4366993029 creator A5085901489 @default.
- W4366993029 creator A5088592256 @default.
- W4366993029 date "2023-06-01" @default.
- W4366993029 modified "2023-10-09" @default.
- W4366993029 title "Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals" @default.
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