Zhang 2019 Redox Biol

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Zhang Y, Bharathi SS, Beck ME, Goetzman ES (2019) The fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase can be a source of mitochondrial hydrogen peroxide. Redox Biol 26:101253.

» PMID: 31234015

Zhang Y, Bharathi SS, Beck ME, Goetzman ES (2019) Redox Biol

Abstract: Fatty acid oxidation (FAO)-driven H2O2 has been shown to be a major source of oxidative stress in several tissues and disease states. Here, we established that the mitochondrial flavoprotein long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H2O2 in vitro by leaking electrons to oxygen. Kinetic analysis of recombinant human LCAD showed that it produces H2O2 15-fold faster than the related mitochondrial enzyme very long-chain acyl-CoA dehydrogenase (VLCAD), but 50-fold slower than a bona fide peroxisomal acyl-CoA oxidase. The rate of H2O2 formation by human LCAD is slow compared to its activity as a dehydrogenase (about 1%). However, expression of hLCAD in HepG2 cells is sufficient to significantly increase H2O2 in the presence of fatty acids. Liver mitochondria from LCAD-/- mice, but not VLCAD-/- mice, produce significantly less H2O2 during incubation with fatty acids. Finally, we observe highest LCAD expression in human liver, followed by kidney, lung, and pancreas. Based on our data, we propose that the presence of LCAD drives H2O2 formation in response to fatty acids in these tissues.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords: Hydrogen peroxide, Mitochondria, Fatty acid oxidation, acyl-CoA dehydrogenase Bioblast editor: Plangger M O2k-Network Lab: CN Tianjin Zhang Y, US PA Pittsburgh Goetzman ES


Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Regulation: Fatty acid  Coupling state: LEAK, OXPHOS  Pathway: F, N, NS  HRR: Oxygraph-2k 

Labels, 2019-07