{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:39:12Z","timestamp":1780547952881,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T00:00:00Z","timestamp":1417478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000094","name":"Ontario Ministry of Agriculture, Food and Rural Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000094","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells. The choline transporter\u2010like protein 1\/solute carrier 44A1 (CTL1\/SLC44A1) and mRNA expression were 2\u20103 times lower in POTS fibroblasts, and choline uptake was reduced 60% (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). Disturbances of membrane homeostasis were observed by reduced ratios between PC:phosphatidylethanolamine and sphingomyelin:cholesterol, as well as by modified phospholipid fatty acid composition. Choline deficiency also impaired mitochondria function, which was observed by a reduction in oxygen consumption, mitochondrial potential, and glycolytic activity. When POTS cells were treated with choline, transporter was up\u2010regulated, and uptake of choline increased, offering an option for patient treatment. The characteristics of the POTS fibroblasts described here represent a first model of choline and CTL1\/SLC44A1 deficiency, in which choline transport, membrane homeostasis, and mitochondrial function are impaired.\u2014Schenkel, L. C., Singh, R. K., Michel, V., Zeisel, S. H., da Costa, K.\u2010A., Johnson, A. R., Mudd, H. S., Bakovic, M. Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 1663\u20101675 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-258566","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T22:28:12Z","timestamp":1417559292000},"page":"1663-1675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts"],"prefix":"10.1096","volume":"29","author":[{"given":"Laila C.","family":"Schenkel","sequence":"first","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratnesh K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Zeisel","sequence":"additional","affiliation":[{"name":"University of North Carolina Nutrition Research Institute Kannapolis North Carolina USA"},{"name":"Department of Nutrition University of North Carolina, Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry\u2010Ann","family":"da Costa","sequence":"additional","affiliation":[{"name":"Toxicology Services Incorporated Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Nutrition University of North Carolina, Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey S.","family":"Mudd","sequence":"additional","affiliation":[{"name":"The Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marica","family":"Bakovic","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.08.013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00009.2009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.03.007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.337"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.1992.10718251"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0005-2736(83)90138-4","article-title":"The effect of choline deficiency on the outer membranes of rat liver mitochondria","volume":"734","author":"Filipowicz C. 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