Show simple item record Kacsó, Gergely Ravasz, Dóra Dóczi, Judit Németh, Beáta Madgar O, Iordanov, Iordan Gál, Anikó Molnár, Mária Judit Nagy, Zsolt Patócs, Attila Balázs Ádám, Veronika Chinopoulos, Christos 2018-09-26T08:42:18Z 2018-09-26T08:42:18Z 2016
dc.identifier 84992561377
dc.identifier.citation pagination=3463-3485; journalVolume=473; journalIssueNumber=20; journalTitle=BIOCHEMICAL JOURNAL;
dc.identifier.uri doi:10.1042/BCJ20160594
dc.description.abstract Succinate-CoA ligase is a heterodimer enzyme composed of Suclg1 -alpha- and a substrate-specific Sucla2 or Suclg2 -beta- subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with, or without methylmalonyl aciduria, in addition to resulting in mitochondrial DNA depletion. We generated mice lacking either one Sucla2 or Suclg2 allele. Sucla2 heterozygote mice exhibited tissue- and age-dependent decreases in Sucla2 expression associated with decreases in ATP-forming activity, but rebound increases in cardiac Suclg2 expression and GTP-forming activity. Bioenergetic parameters including substrate-level phosphorylation were not different between wild type and Sucla2 heterozygote mice unless a submaximal pharmacological inhibition of succinate-CoA ligase was concomitantly present. mtDNA contents were moderately decreased, but blood carnitine esters were significantly elevated. Suclg2 heterozygote mice exhibited decreases in Suclg2 expression but no rebound increases in Sucla2 expression or changes in bioenergetic parameters. Surprisingly, deletion of one Suclg2 allele in Sucla2 heterozygote mice still led to a rebound but protracted increase in Suclg2 expression, yielding double heterozygote mice with no alterations in GTP-forming activity or substrate-level phosphorylation, but more pronounced changes in mtDNA content and blood carnitine esters, and an increase in succinate dehydrogenase activity. We conclude that a partial reduction in Sucla2 elicits rebound increases in Suclg2 expression which is sufficiently dominant to overcome even a concomitant deletion of one Suclg2 allele, pleiotropically affecting metabolic pathways associated with succinate-CoA ligase. These results as well as the availability of the transgenic mouse colonies will be of value in understanding succinate-CoA ligase deficiency.
dc.relation.ispartof urn:issn:0264-6021
dc.title Two transgenic mouse models for beta subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations
dc.type Journal Article 2018-08-02T11:34:53Z
dc.language.rfc3066 en
dc.identifier.mtmt 3099231
dc.identifier.wos 000393756900005
dc.identifier.pubmed 27496549
dc.contributor.department SE/AOK/I/OBI/MTA-SE Neurobiokémiai Kutatócsoport
dc.contributor.department SE/AOK/I/Orvosi Biokémiai Intézet
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote FELTÖLTŐ: Bökönyi Zita -

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