{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:00:23Z","timestamp":1793293223677,"version":"4.5.0"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,24]]},"abstract":"<jats:p>\n                    <jats:italic>SLC25A19<\/jats:italic>\n                    mutations cause Amish lethal microcephaly (MCPHA), which markedly retards brain development and leads to \u03b1-ketoglutaric aciduria. Previous data suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleotide transporter. We generated a knockout mouse model of\n                    <jats:italic>Slc25a19<\/jats:italic>\n                    . These animals had 100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day 10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a yolk sac erythropoietic failure, and elevated \u03b1-ketoglutarate in the amniotic fluid. We found that these animals have normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels, suggesting that transport of these molecules is not the primary role of SLC25A19. We identified thiamine pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through homology searching and confirmed it by using transport assays of the recombinant reconstituted protein. The mitochondria of\n                    <jats:italic>Slc25a19<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and MCPHA cells have undetectable and markedly reduced ThPP content, respectively. The reduction of ThPP levels causes dysfunction of the \u03b1-ketoglutarate dehydrogenase complex, which explains the high levels of this organic acid in MCPHA and suggests that mitochondrial ThPP transport is important for CNS development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0607661103","type":"journal-article","created":{"date-parts":[[2006,10,11]],"date-time":"2006-10-11T21:07:18Z","timestamp":1160600838000},"page":"15927-15932","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":152,"title":["Knockout of\n                    <i>Slc25a19<\/i>\n                    causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia"],"prefix":"10.1073","volume":"103","author":[{"given":"Marjorie J.","family":"Lindhurst","sequence":"first","affiliation":[{"name":"*National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Fiermonte","sequence":"additional","affiliation":[{"name":"Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Struys","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, VU University Medical Center, 1081 HV, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Leonardis","sequence":"additional","affiliation":[{"name":"Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Schwartzberg","sequence":"additional","affiliation":[{"name":"*National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Chen","sequence":"additional","affiliation":[{"name":"*National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Castegna","sequence":"additional","affiliation":[{"name":"Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanda","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, VU University Medical Center, 1081 HV, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[{"name":"*National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,10,24]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10529"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng948"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.031430998"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1099-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf583"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300401200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-7249(03)00053-9"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0580"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.007120"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R300002200"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi184"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-231"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80849-1"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14512"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3249"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.11.875"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.22.6282"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2940293"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)60150-3"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1635259100"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(96)06385-1"},{"key":"e_1_3_4_22_2","first-page":"1464","volume-title":"Methods in Enzymatic Analysis","author":"Gutmann I","year":"1974","unstructured":"I Gutmann, A Wahlefeld Methods in Enzymatic Analysis, ed HU Bergmeyer (Academic, New York), pp. 1464\u20131468 (1974)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0607661103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:40:17Z","timestamp":1649774417000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0607661103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,24]]},"references-count":22,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2006,10,24]]}},"alternative-id":["10.1073\/pnas.0607661103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0607661103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,24]]},"assertion":[{"value":"2006-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}