{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:37:13Z","timestamp":1790329033944,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AG14930"],"award-info":[{"award-number":["AG14930"]}]},{"name":"NIH","award":["1S10RR025449-01"],"award-info":[{"award-number":["1S10RR025449-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reversible post\u2010translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in the structure of proteins; however, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins remain unknown. These studies focused on succinylation of mitochondrial proteins. The results demonstrate that the \u03b1\u2010ketoglutarate dehydrogenase complex (KGDHC) can serve as a trans\u2010succinylase that mediates succinylation in an \u03b1\u2010ketoglutarate\u2010dependent manner. Inhibition of KGDHC reduced succinylation of both cytosolic and mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified KGDHC can succinylate multiple proteins including other enzymes of the tricarboxylic acid cycle leading to modification of their activity. Inhibition of KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex. The much greater effectiveness of KGDHC than succinyl\u2010CoA suggests that the catalysis owing to the E2k succinyltransferase is important. Succinylation appears to be a major signaling system and it can be mediated by KGDHC.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13096-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nReversible post\u2010translation modifications of proteins are common and may regulate many processes. Succinylation of proteins occurs and causes large changes in the structure of proteins. However, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins remains unknown. The results demonstrate that the mitochondrial \u03b1\u2010ketoglutarate dehydrogenase complex (KGDHC) can succinylate multiple mitochondrial proteins and alter their function. Succinylation appears to be a major signaling system and it can be mediated by KGDHC.\n<\/jats:p>","DOI":"10.1111\/jnc.13096","type":"journal-article","created":{"date-parts":[[2015,3,14]],"date-time":"2015-03-14T08:26:49Z","timestamp":1426321609000},"page":"86-96","source":"Crossref","is-referenced-by-count":132,"title":["Alpha\u2010ketoglutarate dehydrogenase complex\u2010dependent succinylation of proteins in neurons and neuronal cell lines"],"prefix":"10.1111","volume":"134","author":[{"given":"Gary E.","family":"Gibson","sequence":"first","affiliation":[{"name":"Brain and Mind Research Institute Weill Cornell Medical College Burke Medical Research Institute White Plains New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Brain and Mind Research Institute Weill Cornell Medical College Burke Medical Research Institute White Plains New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan\u2010Lian","family":"Chen","sequence":"additional","affiliation":[{"name":"Brain and Mind Research Institute Weill Cornell Medical College Burke Medical Research Institute White Plains New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Facility Institute of Biotechnology Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis T.","family":"Denton","sequence":"additional","affiliation":[{"name":"College of Pharmacy Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Facility Institute of Biotechnology Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.207"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20474"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-245241"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.03204.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0503100"},{"key":"e_1_2_7_7_1","article-title":"Reductions in the mitochondrial enzyme a\u2010ketoglutarate dehydrogenase complex in neurodegenerative disease \u2010 beneficial or detrimental?","author":"Chen H. 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