Document Detail


cis-4-decenoic acid provokes mitochondrial bioenergetic dysfunction in rat brain.
MedLine Citation:
PMID:  20540954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Patrícia Fernanda Schuck; Gustavo da Costa Ferreira; Erich Birelli Tahara; Fábio Klamt; Alicia Juliana Kowaltowski; Moacir Wajner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-09
Journal Detail:
Title:  Life sciences     Volume:  87     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-08-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  139-46     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Dehydrogenase / 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:
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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