{"entity": "publication", "iuid": "44993dc1b1d84113a5b844e487253e4d", "timestamp": "2026-08-12T12:36:58.148Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44993dc1b1d84113a5b844e487253e4d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44993dc1b1d84113a5b844e487253e4d"}}, "title": "A pcyt-1 allelic series reveals in vivo consequences of reduced phosphatidylcholine synthesis in C. elegans.", "authors": [{"family": "Qvist", "given": "August", "initials": "A"}, {"family": "Kaper", "given": "Delaney", "initials": "D", "orcid": "0000-0002-9929-8104", "researcher": {"href": "https://publications.scilifelab.se/researcher/e96d29226c884ec496240844de56499a.json"}}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Stjernman", "given": "Albin", "initials": "A"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2026-08-05", "journal": {"title": "G3 (Bethesda)", "issn": "2160-1836", "volume": "16", "issue": "8", "issn-l": "2160-1836"}, "abstract": "Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes and is synthesized in part via the rate-limiting enzyme PCYT1A. In humans, hypomorphic PCYT1A variants cause diverse disorders. To define how graded reductions in PC synthesis affect organismal physiology, we generated and characterized a series of mutant alleles in the Caenorhabditis elegans homolog pcyt-1, including variants corresponding to disease-causing human mutations, as well as an auxin-inducible degradation allele. We identify a clear allelic hierarchy. The V146M variant is embryonic lethal, whereas A97T is largely benign. P154A is temperature-sensitive, and C211Y causes growth delay, reduced brood size, sterility, and lengthened lifespan at standard temperature. Phenotypes of C211Y are rescued by choline, CDP-choline, or PC supplementation, supporting reduced enzymatic function. Lipidomic profiling reveals that decreased PC synthesis consistently increases long-chain polyunsaturated fatty acids (LCPUFAs) in both PCs and phosphatidylethanolamine (PEs) at the expense of shorter saturated species, without markedly altering the PC/PE ratio at 20 \u00b0C. At elevated temperature, the P154A variant exhibits protein instability and a decreased PC/PE ratio. Despite significant lipid remodeling, canonical ER, mitochondrial, and metabolic stress GFP-based reporters are not activated; only the oxidative stress response is elevated, consistent with increased peroxidation-prone LCPUFAs in the pcyt-1 mutant. Acute auxin-induced degradation of PCYT-1 in larvae causes developmental arrest, while acute PCYT-1 degradation in adults disrupts oogenesis, demonstrating a continuous requirement for PC synthesis. Together, these findings establish a functional pcyt-1 allelic series and show that limiting PC synthesis drives compensatory remodeling toward LCPUFA-enriched membranes while rendering the germline particularly vulnerable.", "doi": "10.1093/g3journal/jkag161", "pmid": "42400359", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13439949"}, {"db": "pii", "key": "8724733"}], "notes": [], "created": "2026-08-11T10:58:28.374Z", "modified": "2026-08-11T10:58:28.439Z"}