Difference between revisions of "Kelly 2011 Mitochondrion"
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{{Publication | {{Publication | ||
|title=Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK (2011) The preservation of in vivo phosphorylated and activated uncoupling protein 3 (UCP3) in isolated skeletal muscle mitochondria following administration of 3,4-methylenedioxymethamphetamine (MDMA aka ecstasy) to rats/mice. Mitochondrion. | |title=Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK (2011) The preservation of in vivo phosphorylated and activated uncoupling protein 3 (UCP3) in isolated skeletal muscle mitochondria following administration of 3,4-methylenedioxymethamphetamine (MDMA aka ecstasy) to rats/mice. Mitochondrion. 12: 110-119. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/21453795 PMID:21453795] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/21453795 PMID:21453795] | ||
|authors=Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK | |authors=Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK | ||
|year=2011 | |year=2011 | ||
|journal=Mitochondrion | |journal=Mitochondrion | ||
|abstract=Previous researchers have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) induced hyperthermia, in skeletal muscle of animals, is uncoupling protein 3 (UCP3) dependent. In light of our investigations that in vivo phosphorylation of UCP1 is augmented under conditions of cold-acclimation, we set out to investigate whether (a) UCP3 was phosphorylated in vivo and (b) whether in vivo phosphorylation of UCP3 resulted in increased proton leak following MDMA administration to animals. Our data demonstrate that MDMA treatment (but not PBS treatment) of animals results in both in vivo serine and tyrosine phosphorylation of UCP3 in skeletal muscle mitochondria, isolated in the presence of phosphatase inhibitors to preserve in vivo phosphorylation. In addition, proton leak is only increased in skeletal muscle mitochondria isolated from MDMA treated animals (in the presence of phosphatase inhibitors) and the increased proton leak is due to phosphorylated UCP3. UCP3 abundance in skeletal muscle mitochondria is unaffected by MDMA administration. Preservation of UCP3 phosphorylation and increased proton leak is lost when skeletal muscle mitochondria are isolated in the absence of phosphatase inhibitors. We conclude that MDMA treatment of animals increases proton leak in skeletal muscle mitochondria by activating UCP3 through in vivo covalent modification of UCP3 by phosphorylation. Furthermore, we deduce that the MDMA induced hyperthermia in skeletal muscle is due to increased proton leak in vivo as a result of activation of UCP3 through phosphorylation. | |abstract=Previous researchers have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia, in skeletal muscle of animals, is uncoupling protein 3 (UCP3) dependent. In light of our investigations that ''in vivo'' phosphorylation of UCP1 is augmented under conditions of cold-acclimation, we set out to investigate whether (a) UCP3 was phosphorylated ''in vivo'' and (b) whether ''in vivo'' phosphorylation of UCP3 resulted in increased proton leak following MDMA administration to animals. Our data demonstrate that MDMA treatment (but not PBS treatment) of animals results in both ''in vivo'' serine and tyrosine phosphorylation of UCP3 in skeletal muscle mitochondria, isolated in the presence of phosphatase inhibitors to preserve ''in vivo'' phosphorylation. In addition, proton leak is only increased in skeletal muscle mitochondria isolated from MDMA treated animals (in the presence of phosphatase inhibitors) and the increased proton leak is due to phosphorylated UCP3. UCP3 abundance in skeletal muscle mitochondria is unaffected by MDMA administration. Preservation of UCP3 phosphorylation and increased proton leak is lost when skeletal muscle mitochondria are isolated in the absence of phosphatase inhibitors. We conclude that MDMA treatment of animals increases proton leak in skeletal muscle mitochondria by activating UCP3 through ''in vivo'' covalent modification of UCP3 by phosphorylation. Furthermore, we deduce that the MDMA induced hyperthermia in skeletal muscle is due to increased proton leak ''in vivo'' as a result of activation of UCP3 through phosphorylation. | ||
|keywords= | |keywords=Uncoupling protein, UCP3, Mitochondria, Oxygen consumption, MDMA, Ecstasy, 3,4- methylenedioxymethamphetamine, Proton leak | ||
|mipnetlab=IE Dublin Porter RK | |mipnetlab=IE Dublin Porter RK | ||
}} | }} | ||
| Line 14: | Line 14: | ||
|tissues=Skeletal muscle, Hepatocyte; Liver | |tissues=Skeletal muscle, Hepatocyte; Liver | ||
|preparations=Isolated Mitochondria | |preparations=Isolated Mitochondria | ||
|couplingstates=ETS | |||
|substratestates=CII | |||
|enzymes=Complex I, Complex V; ATP Synthase | |||
|kinetics=Inhibitor; Uncoupler | |||
}} | }} | ||
Revision as of 10:54, 12 February 2013
| Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK (2011) The preservation of in vivo phosphorylated and activated uncoupling protein 3 (UCP3) in isolated skeletal muscle mitochondria following administration of 3,4-methylenedioxymethamphetamine (MDMA aka ecstasy) to rats/mice. Mitochondrion. 12: 110-119. |
Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK (2011) Mitochondrion
Abstract: Previous researchers have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia, in skeletal muscle of animals, is uncoupling protein 3 (UCP3) dependent. In light of our investigations that in vivo phosphorylation of UCP1 is augmented under conditions of cold-acclimation, we set out to investigate whether (a) UCP3 was phosphorylated in vivo and (b) whether in vivo phosphorylation of UCP3 resulted in increased proton leak following MDMA administration to animals. Our data demonstrate that MDMA treatment (but not PBS treatment) of animals results in both in vivo serine and tyrosine phosphorylation of UCP3 in skeletal muscle mitochondria, isolated in the presence of phosphatase inhibitors to preserve in vivo phosphorylation. In addition, proton leak is only increased in skeletal muscle mitochondria isolated from MDMA treated animals (in the presence of phosphatase inhibitors) and the increased proton leak is due to phosphorylated UCP3. UCP3 abundance in skeletal muscle mitochondria is unaffected by MDMA administration. Preservation of UCP3 phosphorylation and increased proton leak is lost when skeletal muscle mitochondria are isolated in the absence of phosphatase inhibitors. We conclude that MDMA treatment of animals increases proton leak in skeletal muscle mitochondria by activating UCP3 through in vivo covalent modification of UCP3 by phosphorylation. Furthermore, we deduce that the MDMA induced hyperthermia in skeletal muscle is due to increased proton leak in vivo as a result of activation of UCP3 through phosphorylation. • Keywords: Uncoupling protein, UCP3, Mitochondria, Oxygen consumption, MDMA, Ecstasy, 3, 4- methylenedioxymethamphetamine, Proton leak
• O2k-Network Lab: IE Dublin Porter RK
Labels:
Organism: Mouse, Rat
Tissue;cell: Skeletal muscle, Hepatocyte; Liver"Hepatocyte; Liver" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
Enzyme: Complex I, Complex V; ATP Synthase"Complex V; ATP Synthase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.
Coupling state: ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
