Endogenous mitochondrial heme homeostasis and trafficking in Saccharomyces Cerevisiae
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Kurtz, Allison Ryan
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Abstract
Heme is a biologically essential yet potentially cytotoxic signaling molecule and cofactor found in nearly all subcellular compartments of eukaryotes. Heme is responsible for many biological processes including transporting and storing gasses, the regulation of transcription and translation, protein synthesis, and assisting redox reactions. Despite the necessity of this molecule, much is still unknown about it, specifically its homeostatic trafficking after biosynthesis. Disruptions in heme homeostasis are correlated with cancers, metabolic diseases, and neurodegenerative disorders. Learning about the regulation of heme homeostasis is essential to treating these diseases. Herein, a genetically encoded ratiometric fluorescent heme sensor (HS1) is used to probe S. cerevisiae for intracellular heme levels in the mitochondria. S. cerevisiae genes are homologous to 23% of human genes, and therefore yeast serves as a model organism for studying gene function. This study consists of interesting HS1 into the mitochondria of knockout S. cerevisiae mutants in various culture conditions to determine the genes responsible for mitochondrial heme trafficking. This research finds six human homologues associated with diseases to consistently have low heme levels. These target genes will allow predictions and further research of genes associated with heme homeostatic regulation in humans.
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Undergraduate Research Option Thesis