{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:28:37Z","timestamp":1777865317389,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,26]]},"group-title":"Cell Biology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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, including retinal dystrophy, lipodystrophy with fatty liver, and spondylometaphyseal dysplasia. To define how graded reductions in PC synthesis affect organismal physiology, we generated and characterized a series of mutant alleles in the\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  homolog\n                  <jats:italic>pcyt-1<\/jats:italic>\n                  , including variants corresponding to disease-causing human mutations, as well as an auxin-inducible degradation (AID) allele.\n                <\/jats:p>\n                <jats:p>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 phosphatidylcholine supplementation, supporting reduced enzymatic function. Lipidomic profiling reveals that decreased PC synthesis consistently increases long-chain polyunsaturated fatty acids (LCPUFAs) in both PCs and 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.<\/jats:p>\n                <jats:p>\n                  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\n                  <jats:italic>pcyt-1<\/jats:italic>\n                  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\n                  <jats:italic>pcyt-1<\/jats:italic>\n                  allelic series and show that limiting PC synthesis drives compensatory remodeling toward LCPUFA-enriched membranes while rendering the germline particularly vulnerable.\n                <\/jats:p>","DOI":"10.64898\/2026.04.22.720214","type":"posted-content","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T22:05:12Z","timestamp":1777241112000},"source":"Crossref","is-referenced-by-count":0,"title":["A\n                  <i>pcyt-1<\/i>\n                  Allelic Series Reveals In Vivo Consequences of Reduced Phosphatidylcholine Synthesis in\n                  <i>C. elegans<\/i>"],"prefix":"10.64898","author":[{"given":"August","family":"Qvist","sequence":"first","affiliation":[{"name":"Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delaney","family":"Kaper","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4202-0339","authenticated-orcid":false,"given":"Marcus","family":"Henricsson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine\/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albin","family":"Stjernman","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Bor\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine\/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3919-2882","authenticated-orcid":false,"given":"Marc","family":"Pilon","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042923151621000_2026.04.22.720214v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065768"},{"key":"2026042923151621000_2026.04.22.720214v1.2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200506124"},{"key":"2026042923151621000_2026.04.22.720214v1.3","doi-asserted-by":"crossref","unstructured":"Bao, X. , M. 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