The uncoupling protein thermogenin during acclimation: indications for pretranslational control.
To analyze the regulation of the content of the uncoupling protein thermogenin in brown adipose tissue, we have selected a physiological transition phase during which to investigate the relationship between the level of mRNA and the level of the ensuing protein product. Mice preacclimated to 28 degrees C were transferred to 4 degrees C. Cold acclimation led to the expected increases in brown fat total protein and RNA content. Two recruited proteins were analyzed: the cytosolic glycerol-3-phosphate dehydrogenase and the mitochondrial uncoupling protein thermogenin. The activity of the dehydrogenase acutely followed the level of the corresponding mRNA, indicating pretranslational control. However, for thermogenin there was a marked time delay between the establishment of the fully recruited level of thermogenin mRNA (after only approximately 4 h of cold exposure) and that of thermogenin itself (after > 3 wk). By reiterative computer simulation, it was investigated whether a model only involving pretranslational regulation could be invoked for either system. For glycerol-phosphate dehydrogenase, a plausible model could be constructed, provided the protein half-life was shorter than approximately 24 h. Despite the long time delay between full thermogenin mRNA recruitment and full thermogenin protein recruitment, a plausible pretranslational control model could also be constructed, provided that the protein half-life was approximately 5 days. This computed value was in good agreement with the half-life obtained from independent thermogenin half-life studies. It is implied that pretranslational control may suffice to explain the regulation of thermogenin content in brown adipose tissue during a warm-to-cold transition period.
Jacobsson
A
A
Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Sweden.
Mühleisen
M
M
Cannon
B
B
Nedergaard
J
J
D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D003080:Cold Temperature; D015342:DNA Probes; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D015342:DNA Probes; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D005993:Glycerolphosphate Dehydrogenase