Date of Award
5-2013
Thesis Date
5-2013
Degree Type
Honors Thesis-Restricted
Degree Name
B.S.
Department
Chemistry
Degree Program
Chemistry
Director
Zhengchang Liu
Abstract
Aconitase is an enzyme of the Krebs cycle that catalyzes the isomerization of citrate to isocitrate. In addition to its enzymatic activity, Aco1 has been reported to bind to mitochondrial DNA (mtDNA) and mediate its maintenance in the budding yeast S. cerevisiae. In the absence of Aco1, cells rapidly lose mtDNA and become “petite” mutants. The purpose of this study is to uncover the mechanism behind mtDNA loss due to an aco1 deletion mutation. We found that an aco1 mutation activates the mitochondria-to-nucleus retrograde (RTG) signaling pathway, resulting in increased expression of citrate synthases (CIT) through the activation of two transcription factors Rtg1 and Rtg3. Increased activity of CIT leads to increased iron accumulation in cells, which is known to raise reactive oxygen species (ROS). By deleting RTG1, RTG3, genes encoding citrate synthases, orMRS3 and MRS4, encoding two irontransporters in the mitochondrial inner membranes, mtDNA loss can be prevented in aco1 deletion mutant cells. We further show that the loss of SOD1, encoding the cytoplasmic isoform of superoxide dismutase, but not SOD2, encoding the mitochondrial isoform of superoxide dismutase, prevents mtDNA loss in aco1 mutant cells. Altogether, our data suggest that mtDNA loss in aco1 mutant cells is caused by the activation of the RTG pathway and subsequent iron accumulation and toxicity in the mitochondria.
Recommended Citation
Farooq, Muhammad Ali, "Iron Citrate Toxicity Causes aco1Δ-induced mtDNA Loss in Saccharomyces cerevisiae" (2013). Senior Honors Theses. 34.
https://scholarworks.uno.edu/honors_theses/34
Rights
The University of New Orleans and its agents retain the non-exclusive license to archive and make accessible this honors thesis in whole or part in all forms of media, now or hereafter known. The author retains all other ownership rights to the copyright of the honors thesis.