Mitochondrial Changes in Ageing Caenorhabditis elegans – What Do We Learn from Superoxide Dismutase Knockouts? (original) (raw)
Figure 8
Results of SOD knockdown/deletion or overexpression according to the model.
Model results showing dependency of mitochondrial superoxide level, hydrogen peroxide production rate and feedback inhibition factor (decrease in energy production relative to n = 0 case) on mitochondrial SOD without feedback (top, n = 0) and with feedback inhibition (bottom, n = 1). WT levels of mitochondrial SOD are normalised to 1 and indicated by the vertical dashed line. The area to the right of WT levels reflects SOD overexpression while the area to the left reflects SOD depletion, with complete knockout corresponding to zero SOD. Note that hydrogen peroxide production rate increases monotonically with SOD. This result is independent of the exact choice of parameters when feedback inhibition is considered (n = 1) as previously observed [50]. The inhibition factor on the third axis is a number between 1.0 and 0.0 that indicates the metabolic depression by feedback inhibition due to mitochondrial uncoupling and inhibition of ETC components by superoxide (relative to the n = 0 case). When the feedback inhibition factor is close to 1.0, metabolism and ROS production are maximal. In particular, when feedback is ignored (n = 0) the factor is 1.0 by definition. Note that, even at WT SOD levels, the feedback factor in the case of n = 1 is approximately 0.62. This can be interpreted as the effect of residual mitochondrial uncoupling, even at WT levels of SOD, which is consistent with the expected basal proton leak through UCP4 [53].