How does thyroid hormone regulate mitochondrial biogenesis in the myocardium?
T4 increases myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis. The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4.  T3 induces mitochondrial biogenesis. In fact, T3 treatment for 72h  increases activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha).  Furthermore, L-T3 increases  the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1α, mitochondrial transcription factor A and peroxisome proliferator activated receptor γ coactivator-1α, in the LV peri-infarct zone.
The activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis by T3. Truncated forms of the nuclear receptor TRα1, with molecular weights of 43 kDa (p43) and 28 Kda have been previously identified in mitochondria. P43 is a mitochondrial T3 receptor which stimulates mitochondrial transcription and protein synthesis in the presence of T3. p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity.