FIG. 2.

Redox stress. The NADH/NAD⁺, NADPH/NADP⁺, and GSH/GSSG redox couples are the major cellular redox buffers. Under unstressed conditions, these three redox couples have adequate capacity to maintain redox homeostasis, termed basal ReBC (X-axis; green box under red line). When cellular ROS levels increase (Left Y-axis; red line), these redox buffers are also able to respond by elevating basal ReBC to a certain level, termed the compensatory ReBC (X-axis; gray area under red line). Under both circumstances, cellular ROS levels are maintained at physiological levels to ensure normal biological function, such as signaling molecule adequacy (Right Y-axis; blue line). However, when this compensatory response continues beyond a certain threshold at which the maximal ReBC is exceeded by cellular reducing of ROS levels (X-axis, black triangle), reductive stress can occur (red line). By contrast, oxidative stress occurs when cellular ReBC decreases (X-axis, black triangle), or/and cellular oxidation of ROS production is overwhelming. Both reductive stress and oxidative stress (collectively named as redox stress) can promote ROS production leading to oxidative damages to macromolecules and perturbations of cellular functions. NAD⁺, nicotinamide adenine dinucleotide; NADH, reduced NAD⁺; NADP⁺, phosphorylated NAD⁺; ReBC, redox buffer capacity; ROS, reactive oxygen species.