BIOGENESIS OF THERMOGENIC MITOCHONDRIA IN BROWN ADIPOSE-TISSUE OF DJUNGARIAN HAMSTERS DURING COLD ADAPTATION

After cold exposure, cytochrome c oxidase (COX) activity increased abo ut 2.5-fold within 2 weeks in the brown adipose tissue (BAT) of Djunga rian hamsters. The mRNAs for COX subunits I and III and the 12 S rRNA, encoded on mitochondrial DNA (mtDNA), as well as mRNAs for COX subuni ts IV, Va and mitochondrial transcription factor A, encoded in the nuc leus, were unchanged when expressed per unit of total tissue RNA. Howe ver, since total tissue RNA doubled per BAT depot, while total DNA rem ained unchanged, the actual levels of these transcripts were increased within BAT cells. In contrast, the abundance of mRNA for uncoupling p rotein was increased 10-fold, indicating specific activation of this g ene. In addition, the maximal rate of protein synthesis analysed in a faithful in organello system was increased 2.5-fold in mitochondria is olated from BAT after 7 days of cold exposure. We conclude from these data that the biogenesis of thermogenic mitochondria in BAT following cold adaptation is achieved by increasing the overall capacity for syn thesis of mitochondrial proteins in both compartments, by increasing t heir mRNAs as well as the ribosomes needed for their translation. In a ddition, the translational rate for COX subunits as well as all other proteins encoded on mtDNA is increased. Thus the pool of subunits enco ded on mtDNA required for assembly of respiratory chain complexes is p rovided. By comparison with other models of increased mitochondrial bi ogenesis, we propose that thyroid hormone (generated within BAT cells by 5'-deiodinase, and induced upon sympathetic stimulation), which is a well known regulator of the biogenesis of mitochondria in many tissu es, is also the major effector of these adaptive changes in BAT.