The role of cholesterol in cancer cell survival:inhibition of Bax-induced apoptosis

Cellular clearance via programmed cell death (apoptosis) is essential for human development and health. Escaping apoptosis is an important hallmark of cancer, and dysregulation of mitochondrial apoptosis is recognized as a common mechanism enabling cancer cell survival and proliferation. While this is often related to upregulation or mutations of the pro-survival protein Bcl-2, another suspected mechanism is related to cholesterol accumulation in the mitochondria of cancer cells due to their altered lipid metabolism. Having established the mechanism by which the apoptotic protein Bax and anti-apoptotic protein Bcl-2 interact with mitochondrial outer membrane mimics using a combination of neutron reflection, ATR-FTIR spectroscopy and solid-state NMR, we now propose to investigate the impact of cholesterol accumulation on the mechanism of apoptosis inhibition in cancer cells.