title: Uncoupled respiration, ROS production, acute lipotoxicity and oxidative damage in isolated skeletal muscle mitochondria from UCP3-ablated mice.
abstract: The function of uncoupling protein 3 (UCP3) is still not established. Mitochondrial uncoupling, control of ROS production, protection against lipotoxicity and protection against oxidative stress are functions classically discussed. To establish a role for UCP3 in these functions, we have here used UCP3 (-/-) mice, backcrossed for 10 generations on a C57Bl/6 background. In isolated skeletal muscle mitochondria, we examined uncoupled respiration, both unstimulated and in the presence of fatty acids. We did not observe any difference between mitochondria from wildtype and UCP3 (-/-) mice. We measured H(2)O(2) production rate and respiration rate under reactive oxygen species-generating conditions (succinate without rotenone) but found no effect of UCP3. We tested two models of acute lipotoxicity-fatty acid-induced oxidative inhibition and fatty acid-induced swelling-but did not observe any protective effect of UCP3. We examined oxidative stress by quantifying 4-hydroxynonenal protein adducts and protein carbonyls in the mitochondria-but did not observe any protective effect of UCP3. We conclude that under the experimental conditions tested here, we find no evidence for the function of UCP3 being basal or induced uncoupling, regulation of ROS production, protection against acute lipotoxicity or protection against oxidative damage.
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: Nabben
authors.forename: Irina G
authors.initials: IG
authors.lastname: Shabalina
authors.forename: Esther
authors.initials: E
authors.lastname: Moonen-Kornips
authors.forename: Denis
authors.initials: D
authors.lastname: van Beurden
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012119:Respiration; D000071247:Uncoupling Protein 3
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3