{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:27:47Z","timestamp":1759336067645,"version":"build-2065373602"},"reference-count":19,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Mayo Clinic Division of Endocrinology and Metabolism"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21CA266999"],"award-info":[{"award-number":["R21CA266999"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016778","name":"Paradifference Foundation","doi-asserted-by":"crossref","award":["HL121079"],"award-info":[{"award-number":["HL121079"]}],"id":[{"id":"10.13039\/100016778","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The rare human neuroendocrine tumors pheochromocytoma and paraganglioma (PPGL) can result from loss of mitochondrial succinate dehydrogenase. The resulting succinate accumulation is tumorigenic in certain neuroendocrine cells. Here, we explore two theoretical approaches to mitigate tumorigenic succinate accumulation in a cell culture model of PPGL. We first study a gene replacement strategy using transposition technology, and conclude that many of the changes in mitochondrial morphology, oxidative cell metabolism and succinate accumulation can be reversed by this process. We then investigate whether riboflavin supplementation has the potential to rescue succinate dehydrogenase activity in the intact SDHA catalytic subunit to suppress succinate accumulation even in the absence of SDHB. We show that this latter strategy is not successful.<\/jats:p>","DOI":"10.1242\/jcs.263925","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:43:31Z","timestamp":1744778611000},"source":"Crossref","is-referenced-by-count":1,"title":["Approaches to reduce succinate accumulation by restoration of succinate dehydrogenase activity in cultured adrenal cells"],"prefix":"10.1242","volume":"138","author":[{"given":"Fatimah","family":"Al Khazal","sequence":"first","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 1 Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leili","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 1 Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Feng","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 2 Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine , , Scottsdale, AZ 85259 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole A.","family":"Becker","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 1 Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford D.","family":"Folmes","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 2 Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine , , Scottsdale, AZ 85259 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Favier","sequence":"additional","affiliation":[{"name":"Inserm, Centre de recherche des Cordeliers, Universit\u00e9 Paris-Cit\u00e9, Sorbonne Universit\u00e9, Equipe Labellis\u00e9e Ligue contre le Cancer 3 , 75006, Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5043-6422","authenticated-orcid":false,"suffix":"III","given":"L. James","family":"Maher","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science 1 Department of Biochemistry and Molecular Biology , , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"2025100108263384900_JCS263925C1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40170-024-00369-9","article-title":"Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma","volume":"12","author":"Al Khazal","year":"2024","journal-title":"Cancer Metab."},{"key":"2025100108263384900_JCS263925C2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1530\/ERC-21-0349","article-title":"A suppressor of dioxygenase inhibition in a yeast model of SDH deficiency","volume":"29","author":"Beimers","year":"2022","journal-title":"Endocr Relat. Cancer"},{"key":"2025100108263384900_JCS263925C3","doi-asserted-by":"crossref","first-page":"e0227033","DOI":"10.1371\/journal.pone.0227033","article-title":"Modeling succinate dehydrogenase loss disorders in C. elegans through effects on hypoxia-inducible factor","volume":"14","author":"Braun","year":"2019","journal-title":"PLoS ONE"},{"key":"2025100108263384900_JCS263925C4","doi-asserted-by":"publisher","first-page":"101416","DOI":"10.1016\/j.beem.2020.101416","article-title":"An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma","volume":"34","author":"Buffet","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"2025100108263384900_JCS263925C5","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1472-6750-7-42","article-title":"Enzymatic engineering of the porcine genome with transposons and recombinases","volume":"7","author":"Clark","year":"2007","journal-title":"BMC Biotechnol."},{"key":"2025100108263384900_JCS263925C6","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/B978-0-12-374814-0.00008-2","article-title":"Transgenic zebrafish using transposable elements","volume":"104","author":"Clark","year":"2011","journal-title":"Methods Cell Biol."},{"key":"2025100108263384900_JCS263925C7","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1089\/108729101753354608","article-title":"Emerging role of riboflavin in the treatment of nucleoside analogue-induced type B lactic acidosis","volume":"15","author":"Dalton","year":"2001","journal-title":"AIDS Patient Care STDS"},{"key":"2025100108263384900_JCS263925C8","doi-asserted-by":"publisher","first-page":"e220373","DOI":"10.1530\/ERC-22-0373","article-title":"Update on the genetics of paragangliomas","volume":"30","author":"Gimenez-Roqueplo","year":"2023","journal-title":"Endocr Relat. Cancer"},{"key":"2025100108263384900_JCS263925C9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/296167","article-title":"Succinate dehydrogenase loss in familial paraganglioma: biochemistry, genetics, and epigenetics","volume":"2015","author":"Her","year":"2015","journal-title":"Int. J. Endocrin."},{"key":"2025100108263384900_JCS263925C10","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ccr.2009.08.013","article-title":"SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling","volume":"16","author":"Kaelin","year":"2009","journal-title":"Cancer Cell"},{"key":"2025100108263384900_JCS263925C11","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1096\/fj.201901456R","article-title":"Succinate dehydrogenase deficiency in a chromaffin cell model retains metabolic fitness through the maintenance of mitochondrial NADH oxidoreductase function","volume":"34","author":"Kluckova","year":"2020","journal-title":"FASEB J."},{"key":"2025100108263384900_JCS263925C12","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.ccr.2013.04.018","article-title":"SDH mutations establish a hypermethylator phenotype in paraganglioma","volume":"23","author":"Letouze","year":"2013","journal-title":"Cancer Cell"},{"key":"2025100108263384900_JCS263925C13","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/s41568-020-00303-3","article-title":"2-Oxoglutarate-dependent dioxygenases in cancer","volume":"20","author":"Losman","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"2025100108263384900_JCS263925C14","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.cmet.2015.12.005","article-title":"Disease-causing SDHAF1 mutations impair transfer of Fe-S clusters to SDHB","volume":"23","author":"Maio","year":"2016","journal-title":"Cell Metab."},{"key":"2025100108263384900_JCS263925C15","doi-asserted-by":"publisher","first-page":"4551","DOI":"10.1016\/j.celrep.2020.03.022","article-title":"TET-mediated hypermethylation primes SDH-deficient cells for HIF2alpha-driven mesenchymal transition","volume":"30","author":"Morin","year":"2020","journal-title":"Cell Rep."},{"key":"2025100108263384900_JCS263925C16","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1024\/0300-9831\/a000225","article-title":"Supplementation with riboflavin (Vitamin B2) for migraine prophylaxis in adults and children: a review","volume":"85","author":"Namazi","year":"2015","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"2025100108263384900_JCS263925C17","doi-asserted-by":"publisher","first-page":"436","DOI":"10.3390\/cancers11040436","article-title":"Pheochromocytomas and paragangliomas: from genetic diversity to targeted therapies","volume":"11","author":"Pang","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2025100108263384900_JCS263925C18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.tig.2008.05.008","article-title":"Iron-sulfur cluster biogenesis and human disease","volume":"24","author":"Rouault","year":"2008","journal-title":"Trends Genet."},{"key":"2025100108263384900_JCS263925C19","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.263925\/3644676\/jcs263925.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.263925\/3647972\/jcs263925.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.263925\/3647972\/jcs263925.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T12:26:39Z","timestamp":1759321599000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/138\/9\/jcs263925\/367936\/Approaches-to-reduce-succinate-accumulation-by"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,1]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,5,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.263925","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"type":"print","value":"0021-9533"},{"type":"electronic","value":"1477-9137"}],"subject":[],"published":{"date-parts":[[2025,5,1]]},"article-number":"jcs263925"}}