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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-07, Vol.397 (3), p.548-552
Main Authors: Sinha, Rohit Anthony, Pathak, Amrita, Mohan, Vishwa, Babu, Satish, Pal, Amit, Khare, Drirh, Godbole, Madan M.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
Bigenomic
Brain - growth & development
Brain - metabolism
Brain development
CEREBELLUM
Cerebellum - growth & development
Cerebellum - metabolism
Cyclooxygenase 1 - genetics
Gene Expression Regulation, Developmental
Genes, Mitochondrial
HYPOTHYROIDISM
Hypothyroidism - genetics
Hypothyroidism - metabolism
MITOCHONDRIA
mTR
NF-E2-Related Factor 1 - metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Prostaglandin-Endoperoxide Synthases - genetics
RATS
Rats, Sprague-Dawley
RECEPTORS
RNA-Binding Proteins - metabolism
Thyroid hormone
THYROID HORMONES
Thyroid Hormones - metabolism
TRANSCRIPTION
Transcription Factors - metabolism
Transcription, Genetic
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Summary: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-1α, NRF-1α 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.05.154