| cis-4-decenoic acid provokes mitochondrial bioenergetic dysfunction in rat brain. | |
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MedLine Citation:
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PMID: 20540954 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: In the present work we investigated the in vitro effect of cis-4-decenoic acid, the pathognomonic metabolite of medium-chain acyl-CoA dehydrogenase deficiency, on various parameters of bioenergetic homeostasis in rat brain mitochondria. MAIN METHODS: Respiratory parameters determined by oxygen consumption were evaluated, as well as membrane potential, NAD(P)H content, swelling and cytochrome c release in mitochondrial preparations from rat brain, using glutamate plus malate or succinate as substrates. The activities of citric acid cycle enzymes were also assessed. KEY FINDINGS: cis-4-decenoic acid markedly increased state 4 respiration, whereas state 3 respiration and the respiratory control ratio were decreased. The ADP/O ratio, the mitochondrial membrane potential, the matrix NAD(P)H levels and aconitase activity were also diminished by cis-4-decenoic acid. These data indicate that this fatty acid acts as an uncoupler of oxidative phosphorylation and as a metabolic inhibitor. cis-4-decenoic acid also provoked a marked mitochondrial swelling when either KCl or sucrose was used in the incubation medium and also induced cytochrome c release from mitochondria, suggesting a non-selective permeabilization of the inner mitochondrial membrane. SIGNIFICANCE: It is therefore presumed that impairment of mitochondrial homeostasis provoked by cis-4-decenoic acid may be involved in the brain dysfunction observed in medium-chain acyl-CoA dehydrogenase deficient patients. |
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Authors:
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Patrícia Fernanda Schuck; Gustavo da Costa Ferreira; Erich Birelli Tahara; Fábio Klamt; Alicia Juliana Kowaltowski; Moacir Wajner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-09 |
Journal Detail:
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Title: Life sciences Volume: 87 ISSN: 1879-0631 ISO Abbreviation: Life Sci. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-08-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 139-46 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl-CoA Dehydrogenase
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deficiency Animals Brain / drug effects*, pathology Cytochromes c / drug effects, metabolism Energy Metabolism / drug effects* Fatty Acids, Monounsaturated / toxicity* Homeostasis / drug effects Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects*, metabolism Mitochondrial Membranes / drug effects, metabolism NADP / drug effects, metabolism Oxidative Phosphorylation / drug effects Oxygen Consumption / drug effects Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Monounsaturated; 505-90-8/4-decenoic acid; 53-59-8/NADP; 9007-43-6/Cytochromes c; EC 1.3.99.3/Acyl-CoA Dehydrogenase |
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