H2O2 release from the very long chain acyl-CoA dehydrogenase.
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 ~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.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
Pâmela A H B
PA
Kakimoto
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
Fábio K
FK
Tamaki
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
Ariel R
AR
Cardoso
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
Sandro R
SR
Marana
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000 São Paulo, SP, Brazil. Electronic address: alicia@iq.usp.br.
Alicia J
AJ
Kowaltowski
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D059305:Diet, High-Fat; D057075:Enzyme Assays; D005260:Female; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D019308:Palmitic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D044942:Acyl-CoA Dehydrogenase, Long-Chain
Acyl-CoA; Fatty acid oxidation; Hydrogen peroxide; Mitochondria