Faculty Sponsor(s)
Megan Bestwick
Location
Jereld R. Nicholson Library: Grand Avenue
Subject Area
Biochemistry
Description
Chronological lifespan assays in yeast rely on promoting a culture’s quiescent stationary phase by calorie restriction, a phase characterized by curtailed overall metabolic rate and a shift from fermentation to mitochondrial respiration. This shift in glucose utilization can be accomplished by reduced TOR (Target of Rapamycin) pathway signaling, a complex regulator of cell growth and cell cycle in which various environmental growth and nutrient signals are integrated to activate or inhibit the Ser/Thr kinase activity of Tor1 protein. Optimal growth conditions promote TOR signaling causing macromolecule biosynthesis, sugar fermentation, increased metabolism, and progression through cell cycle. Many downstream effects of TOR signaling can be silenced by cell treatment with Rapamycin, a drug which binds to Tor1 and inhibits kinase domain function, drastically increasing a cell culture’s chronological lifespan.
Mitochondrial electron transport chain (ETC) machinery, whose activity and expression is modulated by TOR signaling, is the primary site of superoxide formation. Superoxide is a reactive oxygen species (ROS) produced by premature electron leakage directly to oxygen, producing dangerous hydroxyl radicals, via the Haber-Weiss reaction, that diffuse throughout the cell causing damage to DNA, lipid peroxidation, and mitochondrial dysfunction associated with premature cell aging and death most prevalent in neuronal tissue afflicted with neurodegenerative disease.
A primary defense of free radical damage as a respiratory by-product is the neutralization of superoxide by superoxide dismutase 1 (SOD1), which requires copper and zinc as cofactors in the conversion of superoxide to less harmful hydrogen peroxide. Copper is additionally utilized in cytochrome c oxidase as an electron transferring group and is required for the continuous movement of high energy electrons through the ETC, thereby limiting the potential for electron leakage and ROS. Copper, given its two roles in defending against ROS production and induced cell aging, is here modulated by extracellular supplementation to further elucidate its functionality in the context of possible lifespan extension by Rapamycin treatment of SOD1 deletion strains.
Recommended Citation
Walser, Matthew E. and Bestwick, Megan, "Role of Copper and Tor Signaling in Reactive Oxygen Species Induced Cell Aging" (2017). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 9.
https://digitalcommons.linfield.edu/symposium/2017/all/9
Role of Copper and Tor Signaling in Reactive Oxygen Species Induced Cell Aging
Jereld R. Nicholson Library: Grand Avenue
Chronological lifespan assays in yeast rely on promoting a culture’s quiescent stationary phase by calorie restriction, a phase characterized by curtailed overall metabolic rate and a shift from fermentation to mitochondrial respiration. This shift in glucose utilization can be accomplished by reduced TOR (Target of Rapamycin) pathway signaling, a complex regulator of cell growth and cell cycle in which various environmental growth and nutrient signals are integrated to activate or inhibit the Ser/Thr kinase activity of Tor1 protein. Optimal growth conditions promote TOR signaling causing macromolecule biosynthesis, sugar fermentation, increased metabolism, and progression through cell cycle. Many downstream effects of TOR signaling can be silenced by cell treatment with Rapamycin, a drug which binds to Tor1 and inhibits kinase domain function, drastically increasing a cell culture’s chronological lifespan.
Mitochondrial electron transport chain (ETC) machinery, whose activity and expression is modulated by TOR signaling, is the primary site of superoxide formation. Superoxide is a reactive oxygen species (ROS) produced by premature electron leakage directly to oxygen, producing dangerous hydroxyl radicals, via the Haber-Weiss reaction, that diffuse throughout the cell causing damage to DNA, lipid peroxidation, and mitochondrial dysfunction associated with premature cell aging and death most prevalent in neuronal tissue afflicted with neurodegenerative disease.
A primary defense of free radical damage as a respiratory by-product is the neutralization of superoxide by superoxide dismutase 1 (SOD1), which requires copper and zinc as cofactors in the conversion of superoxide to less harmful hydrogen peroxide. Copper is additionally utilized in cytochrome c oxidase as an electron transferring group and is required for the continuous movement of high energy electrons through the ETC, thereby limiting the potential for electron leakage and ROS. Copper, given its two roles in defending against ROS production and induced cell aging, is here modulated by extracellular supplementation to further elucidate its functionality in the context of possible lifespan extension by Rapamycin treatment of SOD1 deletion strains.
