title: Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice.
abstract: The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6:n-3 ratio on liver mitochondrial H(2)O(2) production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6:n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H(2)O(2) production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H(2)O(2) production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I.
authors.affiliation: VM Molecular Biosciences, University of California Davis, Davis, California, United States of America.
authors.forename: Kevork
authors.initials: K
authors.lastname: Hagopian
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Weber
authors.forename: Darren T
authors.initials: DT
authors.lastname: Hwee
authors.forename: Alison L
authors.initials: AL
authors.lastname: Van Eenennaam
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Lluch
authors.forename: José M
authors.initials: JM
authors.lastname: Villalba
authors.forename: Isabel
authors.initials: I
authors.lastname: Burón
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.forename: J Bruce
authors.initials: JB
authors.lastname: German
authors.forename: Steven M
authors.initials: SM
authors.lastname: Watkins
authors.forename: Yana
authors.initials: Y
authors.lastname: Chen
authors.forename: Alfreda
authors.initials: A
authors.lastname: Wei
authors.forename: Roger B
authors.initials: RB
authors.lastname: McDonald
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ramsey
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; C466741:fat-1 protein, C elegans; D006861:Hydrogen Peroxide; D044943:Fatty Acid Desaturases; D042967:Electron Transport Complex I