Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 548-552 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 397 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 2010 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by infrastructure Grant from Department of Science and Technology DST/FIST/LS-II/012/2003 and DST-SERC Grant SR/SO/HS/95/2007 (MMG) and Senior Research. Fellowship [F.NO.10-2 (5)/2003(II)-E.U.II] from Council of Scientific and Industrial Research (RAS), Government of India, New Delhi. We thank Dr. M. Dauca (France) for providing us the RHTII anti-TR antibody.
Keywords
- Bigenomic
- Brain development
- MTR
- Mitochondria
- Thyroid hormone