Oxidative damage and phospholipid fatty acyl composition in skeletal muscle mitochondria from mice underexpressing or overexpressing uncoupling protein 3.
Five markers of different kinds of oxidative damage to proteins [glutamic semialdehyde, aminoadipic semialdehyde, N (epsilon)-(carboxymethyl)lysine, N (epsilon)-(carboxyethyl)lysine and N (epsilon)-(malondialdehyde)lysine] and phospholipid fatty acyl composition were identified and measured in skeletal muscle mitochondria isolated from mice genetically engineered to underexpress or overexpress uncoupling protein 3 (UCP3). Mitochondria from UCP3-underexpressing mice had significantly higher levels of oxidative damage than wild-type controls, suggesting that UCP3 functions in vivo as part of the antioxidant defences of the cell, but mitochondria from UCP3-overexpressing mice had unaltered oxidative damage, suggesting that mild uncoupling in vivo beyond the normal basal uncoupling provides little protection against oxidative stress. Mitochondria from UCP3-underexpressing mice showed little change, but mitochondria from UCP3-overexpressing mice showed marked changes in mitochondrial phospholipid fatty acyl composition. These changes were very similar to those previously found to correlate with basal proton conductance in mitochondria from a range of species and treatments, suggesting that high protein expression, or some secondary result of uncoupling, may cause the observed correlation between basal proton conductance and phospholipid fatty acyl composition.
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, U.K. martin.brand@mrc-dunn.cam.ac.uk
Martin D
MD
Brand
Reinald
R
Pamplona
Manuel
M
Portero-Otín
Jesús R
JR
Requena
Stephen J
SJ
Roebuck
Julie A
JA
Buckingham
John C
JC
Clapham
Susana
S
Cadenas
D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D007473:Ion Channels; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071247:Uncoupling Protein 3
D015415:Biomarkers; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D010743:Phospholipids; D011506:Proteins; D017382:Reactive Oxygen Species; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; C048496:N(6)-carboxymethyllysine; D008239:Lysine