Exogenous thyroid hormones are regulators of cellular metabolism that involves, 
along with other cell structures, mitochondria. Mechanisms of the influence of 
thyroid hormones on the biogenesis of mtDNA are not fully understood due to 
their pleiotropic nature. Different ways of regulation of mitochondrial 
biogenesis by thyroid hormones are discussed in literature, but thyroid 
receptors, localized in both the nucleus and mitochondria, are the main elements 
of most pathways. Data on events occurring after receptor activation are rather 
contradictory. We investigated the degree of involvement of mitochondrial 
transcription factors in the biogenesis of mtDNA induced by triiodothyronine. 
The contribution of TFAM, TFB2M, and helicase Twinkle in thyroid-induced mtDNA 
biogenesis was assessed. The activation of TFAM and TFB2M expression is shown to 
be required for the induction of mtDNA biogenesis. The role of helicase Twinkle, 
the expression induction of which is also observed after triiodothyronine 
addition, remains unclear. The analysis of factors that activate TFAM and TFB2M 
expression showed that NRF-1 is the determinative regulator: deficiency of this 
factor leads to complete collapse of mtDNA biogenesis. However, lack of 
transcriptional coactivator PGC-1α did not lead to significant reduction in 
thyroid-induced biogenesis, whereas literature data point to its key role in the 
biogenesis of mitochondria. Thus, in this study the role of key transcription 
factors in mtDNA biogenesis induced by triiodothyronine was demonstrated for the 
first time in a model system.