Sequential biochemical extraction of stressed cells showed a dramatic shift in TDP43 solubility converting it from a soluble to an insoluble pool under all stress conditions analysed, with arsenitetreated cells showing the most profound change in solubility (Figure 1C). To determine if insoluble TDP43 is reversed upon removal of the stress, arsenitetreated cells were allowed a 2h recovery in full media, which rapidly restored the soluble TDP43 pool (Figure 1D), suggesting that TDP43 solubility is dynamically regulated by oxidative stress. Moreover, the restoration of soluble TDP43 was not due to new protein synthesis, as cycloheximide treatment prior to arsenite addition yielded a similar solubility transition (Figure 1E, lanes 5 that was reversible upon stress recovery (Figure 1E, lanes 9 To evaluate whether stressinduced ROS are responsible for decreased TDP43 solubility, cells were treated with the free radical scavenger Nacetylcysteine (NAC), which completely prevented the arse