Submission Title

Determining the Role of Retinoid x Receptor Alpha in Mitochondrial DNA Transcription

Location

Jereld R. Nicholson Library: Grand Avenue

Subject Area

Biochemistry

Description

Mitochondria are essential organelles for life as it conducts many of the major processes that the cell needs to survive. The production and regulation of ATP, which provides energy to the cells of a living organism, depends on mitochondria and the oxidative phosphorylation (OXPHOS) pathway within mitochondria. Many of the protein subunits within the OXPHOS pathway are encoded in the mitochondrial genome (mtDNA), while the remaining subunits are encoded in the nuclear genome, translated in the cytosol and imported into mitochondria. Transcriptional coordination between these two genomes to produce functional OXPHOS complexes is critical to maintaining cellular homeostasis; therefore, we propose there are mechanisms to coordinate transcription between the two genomes. Retinoid X receptor alpha (RXRα) is a ligand activated nuclear receptor that can also translocate to the mitochondria. It is known that RXRα communicates with the mtDNA; more specifically, it has been confirmed that it plays a role in mtDNA transcription. We aim to determine if RXRα has a direct effect on the rate of transcription of mtDNA. We are currently expressing and purifying the RXRα to use in an in vitro mtDNA transcription assay. The in vitro transcription assay will be used to evaluate the role of RXRα in mitochondrial transcription. In doing so we will better understand the mechanisms that are involved in mtDNA transcription, a critical control point in the generation of the OXPHOS pathway and mitochondrial biogenesis.

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Determining the Role of Retinoid x Receptor Alpha in Mitochondrial DNA Transcription

Jereld R. Nicholson Library: Grand Avenue

Mitochondria are essential organelles for life as it conducts many of the major processes that the cell needs to survive. The production and regulation of ATP, which provides energy to the cells of a living organism, depends on mitochondria and the oxidative phosphorylation (OXPHOS) pathway within mitochondria. Many of the protein subunits within the OXPHOS pathway are encoded in the mitochondrial genome (mtDNA), while the remaining subunits are encoded in the nuclear genome, translated in the cytosol and imported into mitochondria. Transcriptional coordination between these two genomes to produce functional OXPHOS complexes is critical to maintaining cellular homeostasis; therefore, we propose there are mechanisms to coordinate transcription between the two genomes. Retinoid X receptor alpha (RXRα) is a ligand activated nuclear receptor that can also translocate to the mitochondria. It is known that RXRα communicates with the mtDNA; more specifically, it has been confirmed that it plays a role in mtDNA transcription. We aim to determine if RXRα has a direct effect on the rate of transcription of mtDNA. We are currently expressing and purifying the RXRα to use in an in vitro mtDNA transcription assay. The in vitro transcription assay will be used to evaluate the role of RXRα in mitochondrial transcription. In doing so we will better understand the mechanisms that are involved in mtDNA transcription, a critical control point in the generation of the OXPHOS pathway and mitochondrial biogenesis.