title: Thyroid hormone receptor isoforms localize to cardiac mitochondrial matrix with potential for binding to receptor elements on mtDNA.
abstract: 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.
authors.affiliation: Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Morrish
authors.forename: Norman E
authors.initials: NE
authors.lastname: Buroker
authors.forename: Ming
authors.initials: M
authors.lastname: Ge
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Ning
authors.forename: Jesus
authors.initials: J
authors.lastname: Lopez-Guisa
authors.forename: David
authors.initials: D
authors.lastname: Hockenbery
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
mesh_terms: 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
chemical_list: D004272:DNA, Mitochondrial; D008024:Ligands; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine