title: Effect of docosahexaenoic acid on mouse mitochondrial membrane properties.
abstract: Long-chain polyunsaturated (n-3) fatty acids have been proposed to be involved in a wide variety of biological activities. In this study, mitochondrial docosahexaenoic acid (DHA) levels were increased by either dietary manipulation or by fusing the mitochondria with phospholipid vesicles made from 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0/22:6 PC). The fused mitochondria exhibited a DHA-induced decrease in respiratory control index (RCI) and membrane potential and an increase in proton movement. The modified mitochondria also demonstrated an increase in fluidity (as detected by 1,6-diphenyl-1,3,5-hexatriene anisotropy) and changes in membrane structure detected by the fluorescence probes MC540 and pyrene decanoate. Proton movement in lipid vesicles made from mitochondrial lipid extracts was shown to be enhanced by incorporated 18:0/22:6 PC. Mitochondria were isolated from young (5-mon) and old (24-mon) mice which were maintained on either a diet rich in saturated fats (hydrogenated coconut oil) or rich in n-3 polyunsaturated fats (menhaden oil). Mitochondrial bioenergetic function was followed by RCI, state 3 respiration, ATP level, and phosphate uptake. In addition, lipid composition, phospholipid area/molecule and extent of lipid peroxidation were also determined. Decreases in RCI for the menhaden oil diet-modified mitochondria paralleled those in which DHA levels were enhanced by fusion with phospholipid vesicles. RCI reductions are attributed to DHA-induced increases in H+ movement, producing diminished mitochondrial membrane potentials. One purpose of this project was to determine if the deleterious effects of aging on mitochondrial bioenergetic function could be reversed by addition of n-3 fatty acids. The experiments reported here indicate that incorporation of long-chain polyunsaturated n-3 fatty acids into mitochondrial membranes does not appear likely to reverse the effects of age on mitochondrial function.
authors.affiliation: Department of Biology, Indiana University-Purdue University at Indianapolis 46202, USA.
authors.forename: W
authors.initials: W
authors.lastname: Stillwell
authors.forename: L J
authors.initials: LJ
authors.lastname: Jenski
authors.forename: F T
authors.initials: FT
authors.lastname: Crump
authors.forename: W
authors.initials: W
authors.lastname: Ehringer
mesh_terms: D000375:Aging; D000818:Animals; D004042:Dietary Fats, Unsaturated; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D008081:Liposomes; D008297:Male; D008560:Membrane Fluidity; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D011744:Pyrimidinones / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D004042:Dietary Fats, Unsaturated; D005456:Fluorescent Dyes; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D011522:Protons; D011744:Pyrimidinones; D004281:Docosahexaenoic Acids; C003954:merocyanine dye