Copper, ROS, and Mitochondrial Stress: Understanding the Pathways that Govern Metabolic Homeostasis

Cellular respiration is accomplished by the mitochondrial electron transport chain (ETC) that utilizes the movement of high energy electrons, yielded from the breakdown of larger metabolites, to produce usable energy for the cell in the form of ATP. However, this important metabolic process can lead to the production of the cytotoxic by-product superoxide, a member of a class of free radicals known as reactive oxygen species (ROS), which can then react with vital cell components to induce cell dysfunction or apoptosis. The buildup of this ROS-mediated cellular damage over time has strong links to the initiation and progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, and it is therefore imperative to understand the mechanisms that govern its production. To this aim, chronological life span and growth studies were conducted in a S. cerevisiae model, in which we observed strong protective effects against ROS-mediated damage by supplementing cells with exogenous copper. These results suggest that lower concentrations of cellular copper, as a necessary redox co-factor for cytochrome c oxidase in the ETC, may lead to higher rates of ROS production by limiting the number of functional ETC complexes that can properly shuttle electrons