Methylmalonate inhibits succinate-supported oxygen consumption by interfering with mitochondrial succinate uptake

dc.creatorMirandola, SR
dc.creatorMelo, DR
dc.creatorSchuck, PF
dc.creatorFerreira, GC
dc.creatorWajner, M
dc.creatorCastilho, RF
dc.date2008
dc.dateFEB
dc.date2014-11-17T03:51:51Z
dc.date2015-11-26T16:36:10Z
dc.date2014-11-17T03:51:51Z
dc.date2015-11-26T16:36:10Z
dc.date.accessioned2018-03-28T23:18:48Z
dc.date.available2018-03-28T23:18:48Z
dc.identifierJournal Of Inherited Metabolic Disease. Springer, v. 31, n. 1, n. 44, n. 54, 2008.
dc.identifier0141-8955
dc.identifierWOS:000253455400006
dc.identifier10.1007/s10545-007-0798-1
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/56650
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/56650
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/56650
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1271717
dc.descriptionThe effect of methylmalonate (MMA) on mitochondrial succinate oxidation has received great attention since it could present an important role in energy metabolism impairment in methylmalonic acidaemia. In the present work, we show that while millimolar concentrations of MMA inhibit succinate-supported oxygen consumption by isolated rat brain or muscle mitochondria, there is no effect when either a pool of NADH-linked substrates or N,N,N',N'-tetramethyl-p-phenylendiamine (TMPD)/ascorbate were used as electron donors. Interestingly, the inhibitory effect of MMA, but not of malonate, on succinate-supported brain mitochondrial oxygen consumption was minimized when nonselective permeabilization of mitochondrial membranes was induced by alamethicin. In addition, only a slight inhibitory effect of MMA was observed on succinate-supported oxygen consumption by inside-out submitochondrial particles. In agreement with these observations, brain mitochondrial swelling experiments indicate that MMA is an important inhibitor of succinate transport by the dicarboxylate carrier. Under our experimental conditions, there was no evidence of malonate production in MMA-treated mitochondria. We conclude that MMA inhibits succinate-supported mitochondrial oxygen consumption by interfering with the uptake of this substrate. Although succinate generated outside the mitochondria is probably not a significant contributor to mitochondrial energy generation, the physiopathological implications of MMA-induced inhibition of substrate transport by the mitochondrial dicarboxylate. carrier are discussed.
dc.description31
dc.description1
dc.description44
dc.description54
dc.languageen
dc.publisherSpringer
dc.publisherDordrecht
dc.publisherHolanda
dc.relationJournal Of Inherited Metabolic Disease
dc.relationJ. Inherit. Metab. Dis.
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectRat-liver Mitochondria
dc.subjectChain Complex Activities
dc.subjectAcid-induced Convulsions
dc.subjectRespiratory-chain
dc.subjectDicarboxylate Carrier
dc.subjectPermeability Transition
dc.subjectRenal Mitochondria
dc.subjectHeart Mitochondria
dc.subjectTbars Production
dc.subjectGlobus-pallidus
dc.titleMethylmalonate inhibits succinate-supported oxygen consumption by interfering with mitochondrial succinate uptake
dc.typeArtículos de revistas


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