RGD Reference Report - Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development. - Rat Genome Database

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Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development.

Authors: Sinha, RA  Pathak, A  Mohan, V  Babu, S  Pal, A  Khare, D  Godbole, MM 
Citation: Sinha RA, etal., Biochem Biophys Res Commun. 2010 Jul 2;397(3):548-52. doi: 10.1016/j.bbrc.2010.05.154. Epub 2010 May 31.
RGD ID: 10059677
Pubmed: PMID:20515651   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2010.05.154   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGC1AHumancongenital hypothyroidism  ISOPpargc1a (Rattus norvegicus)mRNA:decreased expression:cerebellum (rat)RGD 
Ppargc1aRatcongenital hypothyroidism  IEP mRNA:decreased expression:cerebellum (rat)RGD 
Ppargc1aMousecongenital hypothyroidism  ISOPpargc1a (Rattus norvegicus)mRNA:decreased expression:cerebellum (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)

Genes (Mus musculus)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)

Genes (Homo sapiens)
PPARGC1A  (PPARG coactivator 1 alpha)


Additional Information