cis-4-decenoic acid provokes mitochondrial bioenergetic dysfunction in rat brain.

Abstract

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
• Journal: Life sciences (Life Sci) Vol. 87 Issue 5-6 Pg. 139-46 (Jul 31 2010) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 20540954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Fatty Acids, Monounsaturated
• 4-decenoic acid
• NADP
• Cytochromes c
• Acyl-CoA Dehydrogenase

Topics

• 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