Page 72 - D. Cancer biology
P. 72
[D. Cancer biology-50]
Targeting MFF Induces the Mitochondrial Cell Death via Dissociation
of the Anti-apoptotic Regulator BCL-XL-VDAC Complex in Cancer
Yu Geon Lee¹, Nuri Lim¹, Young Chan Chae¹˙*
¹School of Life Sciences, Ulsan National University of Science and Technology (UNIST), Ulsan 44919, Republic of
Korea
Mitochondria are hubs of multiple cell death pathway including apoptosis and necrosis. These processes mostly
involve a sudden increase in the mitochondrial outer membrane permeability (MOMP). However, how modulators
of mitochondrial cell death are programmed in cancer to promote their survival has not been fully understood. In
our previous study, we identified that mitochondrial fission factor (MFF) formed complex with the voltage-dependent
anion channel (VDAC), a key modulator of MOMP. Here, we have shown that MFF forms heterotrimeric complex
with VDAC and anti-apoptotic BCL-XL protein on mitochondrial outer membrane. This complex is required for cell
death mechanism including release of apoptogenic cytochrome c from mitochondria into cytosol. Accordingly, MFF
regulation to modulate interaction of VDAC with BCL-XL proteins is sufficient to induce mitochondrial cell death
with loss of mitochondrial membrane potential. This finding indicates that mitochondrial fission can be exploited
to couple to the machinery of modulator of mitochondrial cell death including antiapoptotic VDAC-BCL-XL complex
to improve tumor survival.
