Thyroid hormone receptor isoforms localize to cardiac mitochondrial matrix with potential for binding to receptor elements on mtDNA.
Thyroid hormone (T(3)) rapidly promotes both nuclear and mitochondrial DNA transcription in cardiomyocytes, suggesting that T3 directly binds and activates mitochondrial genes. We showed for the first time mitochondrial localization for multiple TRalpha isoforms in heart, including truncated versions. Additionally, we demonstrated novel mitochondrial localization for versions of TRalpha(2), the dominant negative isoform lacking a functional ligand-binding domain. We also confirmed by electromobility shift assays, that TRalpha(2) in mitochondrial extracts binds to thyroid receptor response elements present in the 12S rRNA (DRO) and D-loop region (DR2) of mitochondrial DNA. Thus, TRalpha isoforms may directly regulate T(3) responses at mtDNA in the heart.
Morrish
Fionnuala
F
Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA.
Buroker
Norman E
NE
Ge
Ming
M
Ning
Xue-Han
XH
Lopez-Guisa
Jesus
J
Hockenbery
David
D
Portman
Michael A
MA
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005799:Genes, Dominant; D015151:Immunoblotting; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry*; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry; D014018:Tissue Distribution; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000737:chemistry
D004272:DNA, Mitochondrial; D008024:Ligands; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine