[Voltage-dependent anion channel and hematological malignancies]

Abstract

Voltage-dependent anion channel(VDAC)is mainly located on the outer mitochondrial membrane. High-resolution atomic force microscopy topography shows an eye-shaped VDAC with 3.8 nm x 2.7 nm pore dimensions. New work suggests pore formation by the assembly of homo-oligomers and supramolecule of VDAC or hetero oligomers composed of VDAC and pro-apoptotic proteins, such as Bax. The oligomeric VDAC pore allows for release of cytochrome C. Thus, VDAC plays a central role in the cell life and apoptosis. It has been shown that the hexokinase (HK)-VDAC1 interaction is critical for preventing induction of apoptosis in tumor cells. VDACs are expressed more highly in cancer cells than normal cells, thus can be used as the target in chemotherapy for cancer. VDAC is also involved in pathogenesis of hematological malignancies such as myeloma and chronic lymphocytic leukemia. Following identification of sequence and structure of VDAC, studies have focused on VDAC as important pharmacological target for new anticancer therapy. To induce apoptosis, agents directly interact with VDAC or detach HK from VDAC to disrupt the anti-apoptosis activity of VDAC-HK interaction, such as methyl jasmonate (MJ) and VDAC1-based peptides. In this review, the function, modulation, structure and location of the VDAC, progress of its researches in hematological malignancies and potential as targets of anti-cancer drugs are summarized.