Long-chain 3-hydroxy fatty acids accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial trifunctional protein deficiencies uncouple oxidative phosphorylation in heart mitochondria

dc.creatorTonin, AM
dc.creatorAmaral, AU
dc.creatorBusanello, ENB
dc.creatorGrings, M
dc.creatorCastilho, RF
dc.creatorWajner, M
dc.date2013
dc.dateFEB
dc.date2014-08-01T18:36:01Z
dc.date2015-11-26T18:04:46Z
dc.date2014-08-01T18:36:01Z
dc.date2015-11-26T18:04:46Z
dc.date.accessioned2018-03-29T00:46:57Z
dc.date.available2018-03-29T00:46:57Z
dc.identifierJournal Of Bioenergetics And Biomembranes. Springer/plenum Publishers, v. 45, n. 41671, n. 47, n. 57, 2013.
dc.identifier0145-479X
dc.identifierWOS:000314899500005
dc.identifier10.1007/s10863-012-9481-9
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/81309
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/81309
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1292950
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCardiomyopathy is a common clinical feature of some inherited disorders of mitochondrial fatty acid beta-oxidation including mitochondrial trifunctional protein (MTP) and isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies. Since individuals affected by these disorders present tissue accumulation of various fatty acids, including long-chain 3-hydroxy fatty acids, in the present study we investigated the effect of 3-hydroxydecanoic (3 HDCA), 3-hydroxydodecanoic (3 HDDA), 3-hydroxytetradecanoic (3 HTA) and 3-hydroxypalmitic (3 HPA) acids on mitochondrial oxidative metabolism, estimated by oximetry, NAD(P)H content, hydrogen peroxide production, membrane potential (Delta I) and swelling in rat heart mitochondrial preparations. We observed that 3 HTA and 3 HPA increased resting respiration and diminished the respiratory control and ADP/O ratios using glutamate/malate or succinate as substrates. Furthermore, 3 HDDA, 3 HTA and 3 HPA decreased Delta I, the matrix NAD(P)H pool and hydrogen peroxide production. These data indicate that these fatty acids behave as uncouplers of oxidative phosphorylation. We also verified that 3 HTA-induced uncoupling-effect was not mediated by the adenine nucleotide translocator and that this fatty acid induced the mitochondrial permeability transition pore opening in calcium-loaded organelles since cyclosporin A prevented the reduction of mitochondrial Delta I and swelling provoked by 3 HTA. The present data indicate that major 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies behave as strong uncouplers of oxidative phosphorylation potentially impairing heart energy homeostasis.
dc.description45
dc.description41671
dc.description47
dc.description57
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionPRONEX II
dc.descriptionFAPERGS
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionPROPESQ/UFRGS
dc.descriptionFINEP Rede Instituto Brasileiro de Neurociencia (IBN-Net) [01.06.0842-00]
dc.descriptionInstituto Nacional de Ciencia e Tecnologia, Excitotoxicidade e Neuroprotecao (INCT-EN)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFINEP Rede Instituto Brasileiro de Neurociencia (IBN-Net) [01.06.0842-00]
dc.languageen
dc.publisherSpringer/plenum Publishers
dc.publisherNew York
dc.publisherEUA
dc.relationJournal Of Bioenergetics And Biomembranes
dc.relationJ. Bioenerg. Biomembr.
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectLong-chain 3-hydroxy fatty acids
dc.subjectMitochondria
dc.subjectHeart bioenergetics
dc.subjectOxidative phosphorylation
dc.subjectPermeability transition
dc.subjectRat-liver Mitochondria
dc.subjectMtp Deficiencies
dc.subjectDisorders
dc.subjectInhibition
dc.subjectLchad
dc.subjectAnion
dc.subjectCoa
dc.subjectFibroblasts
dc.subjectGeneration
dc.subjectTransport
dc.titleLong-chain 3-hydroxy fatty acids accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial trifunctional protein deficiencies uncouple oxidative phosphorylation in heart mitochondria
dc.typeArtículos de revistas


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