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Mechanism of action of thyroxine (T4) on the biogenesis of mitochondria using antibiotic-free system: a gerontological survey.

For the biogenesis of mitochondria from rat liver two different genetic systems are responsible, the nucleo-cytoplasmic system, covering 85-90% of the protein, and the mitochondrial system (10-15%). These data have been confirmed by experiment. Both protein fractions were separated by phosphate buffer (pH 11.5), in which only one of them is soluble. The experiments were performed with 3 age groups of rat: 1, 3 and 24 months. The ratio of both protein fractions was not dependent on rat age. The activities of the two genetic systems were examined by the in-vivo incorporation rate of 14 C-leucine. For the mitochondrial genetic system this rate was approximately equal in all of the age groups, while that for the nucleo-cytoplasmic genetic system was reduced in the 24 month group. Hence an age-dependence is demonstrated for the nucleo-cytoplasmic genetic system. The results of our investigation permit the conclusion that the role of the mitochondrial genetic system increases at senescence. To investigate the effect of T4 on the biogenesis of mitochondria, both protein fractions were estimated also in liver of rats treated with T4. The result showed that there was an increase for all the age groups for protein only of nucleo-cytoplasmic origin. Since it is known that T4 stimulates the biogenesis of mitochondria and increases its protein content, it could be inferred that the action of T4 is channelled through the nucleo-cytoplasmic system independent on age, and that the nucleus plays the major regulatory role in the biogenesis of mitochondria.