The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice.
Uncoupling protein 3 (UCP3) is suggested to protect mitochondria against aging and lipid-induced damage, possibly via modulation of reactive oxygen species (ROS) production. Here we show that mice overexpressing UCP3 (UCP3Tg) have a blunted age-induced increase in ROS production, assessed by electron spin resonance spectroscopy, but only after addition of 4-hydroxynonenal (4-HNE). Mitochondrial function, assessed by respirometry, on glycolytic substrate was lower in UCP3Tg mice compared to wild types, whereas this tended to be higher on fatty acids. State 4o respiration was higher in UCP3Tg animals. To conclude, UCP3 overexpression leads to increased state 4o respiration and, in presence of 4-HNE, blunts the age-induced increase in ROS production.
Nabben
Miranda
M
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
Hoeks
Joris
J
Briedé
Jacob J
JJ
Glatz
Jan F C
JF
Moonen-Kornips
Esther
E
Hesselink
Matthijs K C
MK
Schrauwen
Patrick
P
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D019069:Cell Respiration; D007473:Ion Channels / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071247:Uncoupling Protein 3
D000447:Aldehydes; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; C027576:4-hydroxy-2-nonenal