Binding and cytotoxic trafficking of cholesterol hydroperoxides by sterol carrier protein-2.

Redox-active cholesterol hydroperoxides (ChOOHs) generated by oxidative stress in eukaryotic cells may propagate cytotoxic membrane damage by undergoing one-electron reduction or, at low levels, act as mobile signaling molecules like H2O2. We discovered that ChOOHs can spontaneously translocate between membranes or membranes and lipoproteins in model systems, and that this can be accelerated by sterol carrier protein-2 (SCP-2), a nonspecific lipid trafficking protein. We found that cells overexpressing SCP-2 were more susceptible to damage/toxicity by 7α-OOH (a free radical-generated ChOOH) than control cells, and that this correlated with 7α-OOH delivery to mitochondria. The methods used for obtaining these results and for establishing that cellular SCP-2 binds and traffics 7α-OOH are described in this chapter.