H2O2 release from the very long chain acyl-CoA dehydrogenase

Redox Biology
Pâmela A H B KakimotoAlicia J Kowaltowski

Abstract

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.

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Citations

Jan 31, 2016·Redox Biology·Pâmela A Kakimoto, Alicia J Kowaltowski
Jan 8, 2016·Redox Biology·Celia QuijanoAndrés Trostchansky
Mar 4, 2020·Infection and Immunity·Catherine D Shelton, Mariana X Byndloss
Jun 6, 2020·Antioxidants·Ryan J Mailloux
Nov 19, 2019·Oxidative Medicine and Cellular Longevity·Helen KaiserMark W Hamrick
Jul 26, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Lara Ferreira AzevedoFernando Barbosa
Nov 2, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bernard Fromenty
Jan 1, 2021·Free Radical Biology & Medicine·Chidozie N OkoyeCollins Kamunde
Dec 25, 2019·Annals of Hepatology·S M Touhidul IslamInderjit Singh
Mar 12, 2020·Free Radical Biology & Medicine·Ze ChenHongliang Li
Apr 6, 2021·American Journal of Physiology. Endocrinology and Metabolism·Cody D SmithP Darrell Neufer
Sep 3, 2018·Free Radical Biology & Medicine·Anibal E VercesiEstela N B Busanello
Aug 22, 2021·Antioxidants & Redox Signaling·Eftekhar Eftekharpour, Paul Fernyhough
Aug 28, 2021·Biomolecules·Ana Karina Aranda-RiveraJosé Pedraza-Chaverri

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Methods Mentioned

BETA
PCR
protein assay

Software Mentioned

GraphPad Prism
OriginLab

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