ArticleCell metabolism2023
Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Heme as a versatile signaling molecule: Coordinating mitochondrial metabolism with global cellular responses.The Journal of biological chemistry · 2026Review
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- A conserved vesicular circuit enables metabolic adaptation and maintains systemic heme homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Expanding the ocular and genetic spectrum of FLVCR1-associated disease in a Chinese cohort.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.Science (New York, N.Y.) · 2026Article
- Diverse high-fat diets drive multi-omic reprogramming that persists after dietary reversal.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.bioRxiv : the preprint server for biology · 2026Article
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- The regulatory roles and therapeutic strategies of the solute carrier transporters in cancer metabolism.NPJ precision oncology · 2026Review
- FLVCR1-related diseases: from clinical heterogeneity to mechanistic insights.Brain communications · 2026Review
- Homeostatic response of phospholipid pathways to PCYT2 deficiency and impaired de Novo synthesis of phosphatidylethanolamine.Scientific reports · 2025Article
- Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis.Cell metabolism · 2025Article
- SPNS1 variants cause multiorgan disease and implicate lysophospholipid transport as critical for mTOR-regulated lipid homeostasis.The Journal of clinical investigation · 2025Article
- A Genome-Wide Association Study of Circulating Serum Choline, Betaine, Dimethylglycine, and Their Ratios.Nutrients · 2025Article
- HIF-independent oxygen sensing via KDM6A regulates ferroptosis.Molecular cell · 2025Article
- Riboflavin drives nucleotide biosynthesis and iron-sulfur metabolism to promote acute myeloid leukemia.bioRxiv : the preprint server for biology · 2025Article
- PNPLA6 regulates retinal homeostasis by choline through phospholipid turnover.Nature communications · 2025Article
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12 authors at 3 institutions in 1 country.
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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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.