Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development.
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.
Sinha
Rohit Anthony
RA
Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Pathak
Amrita
A
Mohan
Vishwa
V
Babu
Satish
S
Pal
Amit
A
Khare
Drirh
D
Godbole
Madan M
MM
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D050259:Genes, Mitochondrial; D007037:Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D051265:NF-E2-Related Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3