Figure 1. The Redox-optimized ROS balance hypothesis.

The plot illustrates that the extent of ROS imbalance is defined by the overall intracellular and intramitochondrial redox environments (see text and Fig. 2). Physiological ROS signaling (denoted between dashed lines) occurs within a range close to the minimum of the overall (red) curve that corresponds to intermediate values of the redox environment. Oxidative stress can happen at either extreme of redox potential, that is, when the intracellular and/or intramitochondrial environments are either highly reduced or highly oxidized.

Away from the minimum, the extent of ROS overflow in the system is governed by completely different mechanisms at the two redox extremes. Under a more reduced redox environment (towards the right hand side of the plot), ROS overflow increases because ROS (O₂^.−, H₂O₂) production (blue line) will be favored, exceeding the scavenger capacity, even though the latter is at its maximum level (green line). At more oxidized redox potentials (left hand side), ROS overflow occurs as a consequence of depletion of the ROS scavengers pool. See text for further details.