H2O2 release from the very long chain acyl-CoA dehydrogenase

Autor(es)

Kakimoto, Pamela A. H. B. ^[1] ; Tamaki, Fabio K. ^[1] ; Cardoso, Ariel R. ^[1] ; Marana, Sandro R. ^[1] ; Kowaltowski, Alicia J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: REDOX BIOLOGY; v. 4, p. 375-380, APR 2015.
• Citações Web of Science: 7

Resumo

Enhanced mitochondrial generation of oxidants, including hydrogen peroxide (H2O2), is related to a large number of pathological conditions, including diet-induced obesity and steatohepatosis. Indeed, we have previously shown that high fat diets increase the generation of H2O2 in liver mitochondria energized by activated fatty acids. Here, we further study fatty-acid induced H2O2 release in liver mitochondria, and determine the characteristics that regulate it. We find that this production of H2O2 is independent of mitochondrial inner membrane integrity and insensitive to purine nucleotides. On the other hand, palmitate-induced H2O2 production is strongly enhanced by high fat diets and is pH-sensitive, with a peak at a matrix pH of similar to 8.5. Using recombinantly expressed human very long chain acyl-CoA dehydrogenase, we are able to demonstrate that palmitate-induced H2O2 release may be ascribed to the activity of this enzyme alone, acting as an oxidase. Our results add to a number of findings indicating that sources outside of the electron transport chain can generate significant, physiopathologically relevant, amounts of oxidants in mitochondria. (C) 2015 The Authors. Published by Elsevier B.V. (AU)

• Processo FAPESP: 12/50500-7 - Estudo do envolvimento da sinalização retrógrada RTG-dependente na manutenção da atividade mitocondrial durante o envelhecimento de Saccharomyces cerevisiae
• Beneficiário: Fernanda Marques da Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs