PMID- 21453795
OWN - NLM
STAT- MEDLINE
DCOM- 20120523
LR  - 20161125
IS  - 1872-8278 (Electronic)
IS  - 1567-7249 (Linking)
VI  - 12
IP  - 1
DP  - 2012 Jan
TI  - 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.
PG  - 110-9
LID - 10.1016/j.mito.2011.03.011 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier B.V. and Mitochondria Research Society. All rights 
      reserved.
FAU - Kelly, Orlagh M
AU  - Kelly OM
AD  - School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
FAU - McNamara, Yvonne M
AU  - McNamara YM
FAU - Manzke, Lars H
AU  - Manzke LH
FAU - Meegan, Mary J
AU  - Meegan MJ
FAU - Porter, Richard K
AU  - Porter RK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110329
PL  - Netherlands
TA  - Mitochondrion
JT  - Mitochondrion
JID - 100968751
RN  - 0 (Hallucinogens)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Ucp3 protein, mouse)
RN  - 0 (Ucp3 protein, rat)
RN  - 0 (Uncoupling Protein 3)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Female
MH  - Hallucinogens/administration & dosage/*metabolism
MH  - Ion Channels/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*drug effects/*metabolism
MH  - Mitochondrial Proteins/*metabolism
MH  - Muscle, Skeletal/*drug effects/*metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Serine/metabolism
MH  - Tyrosine/metabolism
MH  - Uncoupling Protein 3
EDAT- 2011/04/02 06:00
MHDA- 2012/05/24 06:00
CRDT- 2011/04/02 06:00
PHST- 2010/11/16 00:00 [received]
PHST- 2011/03/11 00:00 [revised]
PHST- 2011/03/15 00:00 [accepted]
PHST- 2011/04/02 06:00 [entrez]
PHST- 2011/04/02 06:00 [pubmed]
PHST- 2012/05/24 06:00 [medline]
AID - S1567-7249(11)00049-3 [pii]
AID - 10.1016/j.mito.2011.03.011 [doi]
PST - ppublish
SO  - Mitochondrion. 2012 Jan;12(1):110-9. doi: 10.1016/j.mito.2011.03.011. Epub 2011 
      Mar 29.