2015 Beckman Symposium   

Jennifer Sun

Presentation Date:

Jennifer Sun

09 - Uncovering Part of Calcium's Role in Modulating the Function of the Human Cardiac Voltage-Gated Sodium Channel

Vanderbilt University


Although a majority of the genes that encode mitochondrial proteins are found in the nucleus of eukaryotic cells, mitochondria have maintained their own genomes that replicate independently of the rest of the cell. Because of this, coordination between the mitochondrial and nuclear genomes is essential for maximizing the fitness of the organism and for maintaining proper regulation of cellular functions. Many mutations in both nuclear- and mtDNA-encoded genes are responsible for a growing list of metabolic disorders. However, the network of mito-nuclear gene interactions is not yet well understood. The goal of this project is to examine the role that genes encoded in the mtDNA play in hypoxia response. Since mitochondria are the primary consumers of oxygen in the cell, there exist signaling pathways between the mitochondria and nucleus that coordinate switches in metabolism as well as other processes to mediate the effects of hypoxia. Hypoxia tolerance is also relevant to a number of medical conditions, including heart disease, stroke, preterm births, and cancer. Here, we use a mito-nuclear introgression model in Drosophila, where foreign mtDNAs have been combined with a defined nuclear genetic background, as a means to study mitochondrial genetic effects on the nuclear transcriptional response to hypoxia. We investigate this system under various lengths of hypoxic exposure and carry out transcriptome analysis through RNA-seq. Our findings indicate that transcription of nuclear genes is modified by mtDNA in response to hypoxia, and that alternative mtDNAs influence different sets of nuclear genes in their transcriptional response. These observations identify novel mito-nuclear signaling responses to altered oxygen environments.

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