UCP1 muscle gene transfer and mitochondrial proton leak mediated thermogenesis.
Mitochondrial uncoupling protein 1 (UCP1) mediates the thermogenic transport of protons through the inner mitochondrial membrane. This proton leak uncouples respiration from ATP synthesis. The current study assessed the possible contribution of UCP1 muscle gene transfer to impair mitochondrial respiration in a tissue lacking UCP1 gene expression. Rats received an intramuscular injection of plasmid pXC1 containing UCP1 cDNA in the right tibialis muscles, while left tibialis muscles were injected with empty plasmid as control. Ten days after DNA injection, mitochondria from tibialis anterior muscles were isolated and analyzed. UCP1 gene transfer resulted in protein expression as analyzed by inmunoblotting. Mitochondria isolated from UCP1-injected muscles showed a significant increase in state 2 and state 4 oxygen consumption rates and a decreased respiration control ratio in comparison to mitochondria from control muscles. Furthermore, UCP1-containing mitochondria had a lower membrane potential in those states (2 and 4) when compared with control mitochondria. Our results revealed that UCP1 muscle gene transfer is associated with an induced mitochondrial proton leak, which could contribute to increase energy expenditure.
Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Eider
E
Larrarte
Javier
J
Margareto
Francisco J
FJ
Novo
Amelia
A
Marti
J
J
Alfredo Martínez
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007473:Ion Channels; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis / Q000502:physiology*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011522:Protons; D012333:RNA, Messenger; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D000255:Adenosine Triphosphate