Thyroid Hormone Receptor Alpha in Mitochondrial Transcription

Subject Area

Biochemistry and Molecular Biology

Description

Mitochondrial DNA (mtDNA) encodes core proteins in the electron transport and oxidative phosphorylation pathway. The remaining subunits of these protein complexes are encoded in the nuclear genome, translated in the cytosol and imported into mitochondria. Transcription of mtDNA transcription is achieved with three core factors: mitochondrial RNA polymerase (POLMRT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factor B2 (TFB2M). Regulation of this process requires additional proteins, and likely transcriptional coordination with the nuclear genome. We propose that the thyroid hormone receptor alpha (THRA) acts to coordinate transcription between the two genomes. The thyroid hormone, triiodothyronine (T3), increases mitochondrial biogenesis through the activation of the THRA protein. This protein is a ligand activated nuclear receptor that can also translocate to the mitochondria. We aim to determine if THRA has a direct effect on the rate of transcription of mtDNA. We are currently expressing and purifying the THRA protein for in vitro assays. Understanding the role of THRA in mtDNA transcription will lead to a better understanding of the mechanisms generating of the OXPHOS pathway complexes and mitochondrial biogenesis.

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Thyroid Hormone Receptor Alpha in Mitochondrial Transcription

Mitochondrial DNA (mtDNA) encodes core proteins in the electron transport and oxidative phosphorylation pathway. The remaining subunits of these protein complexes are encoded in the nuclear genome, translated in the cytosol and imported into mitochondria. Transcription of mtDNA transcription is achieved with three core factors: mitochondrial RNA polymerase (POLMRT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factor B2 (TFB2M). Regulation of this process requires additional proteins, and likely transcriptional coordination with the nuclear genome. We propose that the thyroid hormone receptor alpha (THRA) acts to coordinate transcription between the two genomes. The thyroid hormone, triiodothyronine (T3), increases mitochondrial biogenesis through the activation of the THRA protein. This protein is a ligand activated nuclear receptor that can also translocate to the mitochondria. We aim to determine if THRA has a direct effect on the rate of transcription of mtDNA. We are currently expressing and purifying the THRA protein for in vitro assays. Understanding the role of THRA in mtDNA transcription will lead to a better understanding of the mechanisms generating of the OXPHOS pathway complexes and mitochondrial biogenesis.