{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:19Z","timestamp":1787005759162,"version":"build-2736575974"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005189","name":"HM | Estonian Research Competency Council","doi-asserted-by":"publisher","award":["1289"],"award-info":[{"award-number":["1289"]}],"id":[{"id":"10.13039\/501100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK117396 and R01 DK071865"],"award-info":[{"award-number":["R01 DK117396 and R01 DK071865"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008369","name":"Sihtasutus Archimedes","doi-asserted-by":"publisher","award":["Dora Plus 1.2 and Kristjan Jaak Scholarship Programmes"],"award-info":[{"award-number":["Dora Plus 1.2 and Kristjan Jaak Scholarship Programmes"]}],"id":[{"id":"10.13039\/100008369","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:p>\n                    \u03b1-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuel production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of\n                    <jats:italic>\n                      Atp7a\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu but instead increased selenium levels that were low in\n                    <jats:italic>\n                      Atp7a\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with an improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of a Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2305961120","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:35:57Z","timestamp":1695742557000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["\u03b1-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8427-1649","authenticated-orcid":false,"given":"Ekaterina","family":"Kabin","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn 12618, Estonia"},{"name":"Department of Physiology, Johns Hopkins Medical Institutes, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins Medical Institutes, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-7723","authenticated-orcid":false,"given":"Shubhrajit","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins Medical Institutes, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn 12618, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-8097","authenticated-orcid":false,"given":"Joshua W.","family":"Smith","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Core, Johns Hopkins Medical Institutes, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-0242","authenticated-orcid":false,"given":"Martina","family":"Ralle","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health &amp; 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