FIGURE 4.

Regulation of ROS production and ATP synthesis by PmitoK_ATP under control and hyperosmotic stress conditions. (A) Under control conditions, a basal production of activators occurs, whereas ATP is produced at high level; as a consequence, in the balance of modulators, ATP inhibition of the PmitoK_ATP activity prevails, thus allowing only a basal channel activity. (B) Under moderate stress conditions, an increase in the mitochondrial generation of ROS occurs that activates PmitoK_ATP, which, in turn, according to a feedback mechanism, may dampen excess ROS production. Moreover, an activation of the mitochondrial PLA₂ also occurs, that may increase the in vivo production of FFAs/acyl-CoAs, which further enhance channel activation. On the other hand, channel inhibition by ATP may represent a brake able to finely regulate the K⁺ cycle, so that ΔΨ is strongly decreased to control ROS, but the ATP synthesis is not impaired. In this manner, PmitoK_ATP meets the cell needs, i.e., to dampen harmful ROS production to curtail oxidative stress and, at the same time, to preserve energy to counteract stress. (C) Severe stress conditions determine a further increase in the ROS generation, as well as in the PLA₂ activity, which, in turn, may increase the in vivo production of FFAs/acyl-CoAs. Under these conditions, the balance between channel modulators favors stronger channel activation by activators over inhibition by ATP. This further increased PmitoK_ATP activity determines a ΔΨ collapse able to counteract large-scale ROS production, but, in this case, it leads to a strong decrease in the ATP synthesis, although not complete impairment is observed. For details, see the text. The continuous or dotted arrows refer to a more or less active pathway, respectively.