Oxidative stress as an essential modulator of Bax apoptotic activity: molecular insights by single-molecule fluorescence
Activation of the protein Bax leads to its aggregation, formation of pores in mitochondrial outermembranes and irretrievably to cellular death (apoptosis). This process can be modulated by oxidative stress, which generates oxidized phospholipids as a result of irreversible oxidation of unsaturated fatty acids. This project aims at elucidating in which way oxidative stress influences pro-apoptotic activity of Bax on molecular level. We have selected two essential modulators of apoptotic activity that are connected with oxidative stress- oxidized phospholipids and bile acids. In order to see how these two totally different classes of compounds influence Bax tendency to oligomerize on model lipid bilayers and to form membrane pores we will apply modern single-molecule fluorescence techniques. This strategy may help to uncover a general mechanism by which Bax irretrievably triggers the apoptosis.