Hypothyroidism during early mammalian brain development is associated with 
decreased expression of various mitochondrial encoded genes along with evidence 
for mitochondrial dysfunction. However, in-spite of the similarities between 
neurological disorders caused by perinatal hypothyroidism and those caused by 
various genetic mitochondrial defects we still do not know as to how thyroid 
hormone (TH) regulates mitochondrial transcription during development and 
whether this regulation by TH is nuclear mediated or through mitochondrial TH 
receptors? We here in rat cerebellum show that hypothyroidism causes reduction 
in expression of nuclear encoded genes controlling mitochondrial biogenesis like 
PGC-1alpha, NRF-1alpha and Tfam. Also, we for the first time demonstrate a 
mitochondrial localization of thyroid hormone receptor (mTR) isoform in 
developing brain capable of binding a TH response element (DR2) present in 
D-loop region of mitochondrial DNA. These results thus indicate an integrated 
nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by 
TH during brain development.