Amaral 2016 Biochim Biophys Acta

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Publications in the MiPMap
Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M (2016) cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca2+ homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency. Biochim Biophys Acta 1857:1363-72.

Β» PMID: 27240720 Open Access

Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M (2016) Biochim Biophys Acta

Abstract: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca2+ retention capacity in Ca2+-loaded brain and liver mitochondria. The reduction of Ca2+ retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca2+. Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency.

Copyright Β© 2016 Elsevier B.V. All rights reserved. β€’ Keywords: Medium-chain acyl-CoA dehydrogenase deficiency, Medium-chain acylcarnitines, Medium-chain fatty acids, Mitochondrial dysfunction, Mitochondrial permeability transition, Safranin

β€’ O2k-Network Lab: BR Porto Alegre Souza DOG

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Permeability transition, Oxidative stress;RONS  Organism: Rat  Tissue;cell: Nervous system, Liver  Preparation: Isolated mitochondria  Enzyme: Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase  Regulation: Inhibitor, Uncoupler, Fatty acid  Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k 


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