The Role Of Copper-sensing MAC1 In Defense Against Oxidative Stresses

Copper is an essential micronutrient to almost all living organisms and plays critical roles in a number of physiological processes. Copper deficiency can negatively affect even disrupt those important physiological processes. However, when copper is in excess, it can participate in Fenton-like reactions producing highly reactive free radicals such as hydroxyl radicals HO'. Hydroxyl radicals are able to damage almost all biochemical chemical molecules including DNAs and proteins. Therefore, cells must balance the intracellular copper level so that it is not too high and not too low. Copper homeostasis in the budding yeast Saccharomyces cerevisiae is established mainly through controlling copper uptake. Macl is a copper-sensing transcription factor that regulates the genes important for yeast copper uptake and plays a critical role in copper homeostasis. Deletion of MAC1 gene will render cells unable to undergo respiration and sensitive to heat and oxidative stresses. Addition of exogenous Cu2+ ions can enable the mutant cells to respire and alleviate the sensitivities to stresses. The goal of the current thesis is to investigate mechanism by which Macl defends yeast cells against heat and oxidative stresses. Yeast mutant of MAC1 deletion was used to determine whether or not MAC1 influences the expression of heat shock protein HSP104 and anti-oxidative gene CTT1. Data reported here show that Mac1 likely acted not by affecting the expression of HSP104 or CTT1, rather by a novel mechanism yet to be determined.