To further dissect the pathways involved in P110‐induced benefits observed in ALS patient‐derived fibroblasts, we focused on motor neurons expressing G93A SOD1 mutation using two stressors: serum starvation for 72 h or H2O2 injury. NSC34, a motor neuron‐like cell line expressing human G93A SOD1, compared to cells expressing the human WTSOD1, has a significant increase in cytosolic oxidative stress. SOD1 G93A cells showed an approximately twofold increase in mitochondrial ROS (Fig 2A, P = 0.001), which was reduced when SOD1 G93A cells were treated with P110 in a dose‐dependent manner (Figs 2A and EV2A; P = 0.003). The ability to concentrate the TMRM probe in mitochondria was decreased in SOD1 G93A (indicative of loss mitochondrial membrane potential; P = 0.003) that was also improved by P110 treatment in a dose‐dependent manner (Figs 2A and EV2A). A causal role for endogenous nitric oxide (NO) in motor neurons and apoptosis expressing mutant SOD1 has been reported (Lee et al, 2009). As expected, we also observed a significant increase in NO levels in SOD G93A cells (under serum starvation as an additional stressor; P = 0.0395), which were significantly reduced by P110 treatment; limiting mitochondrial dysfunction was sufficient to reduce NO levels from 198% in hSOD1 G93A without to 145% with P110 (P = 0.044; Fig EV2A). This was associated with a twofold increase in cell necrosis (measured by LDH release) in mutant SOD1 cells, which was significantly reduced by P110 treatment (Fig EV2A; P = 0.0014). Similar effect was observed following acute H2O2 treatment instead of serum starvation (Fig EV2B).