Thermodynamic Stability of an Aging Proteome
How much oxidative damage can a proteome withstand before a critical threshold is reached? What defines this threshold? The accumulation of oxidized protein is a universal feature of an aging organism, however a quantitative understanding of the effects of physiological levels of oxidation on proteome stability is lacking.Taking advantage of a growing body of data on length, charge, and stability distributions of entire proteomes, we develop a first-principles thermodynamic model of the effects of oxidation on the stability of proteins within an aging cell. By determining the equilibrium fraction of unfolded protein as a function of both oxidative stress and temperature, we predict that a small subset of proteins is largely responsible for straining an organism's protein homeostasis machinery. Furthermore, by looking at functional enrichment within this subset, we identify the protein classes that are expected to be the most sensitive to oxidation-induced destabilization.