Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice.
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.
Hagopian
Kevork
K
VM Molecular Biosciences, University of California Davis, Davis, California, United States of America.
Weber
Kristina L
KL
Hwee
Darren T
DT
Van Eenennaam
Alison L
AL
López-Lluch
Guillermo
G
Villalba
José M
JM
Burón
Isabel
I
Navas
Plácido
P
German
J Bruce
JB
Watkins
Steven M
SM
Chen
Yana
Y
Wei
Alfreda
A
McDonald
Roger B
RB
Ramsey
Jon J
JJ
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
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