Figure 2.

Redox-Optimized ROS Balance and the effect of oxidative stress on mitochondrial respiration, H₂O₂ emission, and the RE. R-ORB postulates that ROS levels (as the net result of production and scavenging) depend on the intra-cellular and -mitochondrial redox environment (RE). It also proposes that there is a minimum level of ROS emission when mitochondria maximize their energetic output. Under high energy demand, and despite large respiratory rates, ROS emission levels will be kept to a minimum by ROS scavenging systems (Stanley et al., 2011; Aon et al., 2012). Oxidative stress can happen at either extreme of RE, either highly reduced or highly oxidized, but governed by different mechanisms (Aon et al., 2010; Kembro et al., 2014). The plot displays schematically the summary of the response of respiration (black traces) and ROS emission in stressed mitochondria (gray traces) plus further addition of the uncoupler FCCP (dashed-dotted line). Continuous lines correspond to the absence of stress whereas dashed lines belong to mitochondria under stressed conditions (Cortassa et al., 2014). Black arrows indicate the direction of change in VO₂ and ROS elicited by stress. Notice the shift toward more oxidized RE in the curves corresponding to stressful conditions. The thick gray arrow pointing to the left denotes pathological conditions arising, e.g., from chronic diseases, where severe stress will affect both energetic (e.g., ΔΨ_m, ADP consumption) and redox [e.g., NAD(P)H, GSH, Trx] functions thus increased mitochondrial ROS emission and higher cytoplasmic ROS levels. Reprinted from Cortassa et al. (2014).