Modulation of the mitochondrial voltage dependent anion channel (VDAC) by curcumin

• Curcumin induces closure of human VDAC-1.
• Curcumin-treated VDAC showed lower single channel conductance.
• Amino acid residues in N-terminus and channel wall of VDAC interact with curcumin.
• Curcumin-induced apoptosis is possibly associated with VDAC-closure.

Voltage dependent anion channel (VDAC) of mitochondria plays a crucial role in apoptosis. Human VDAC-1, reconstituted in planar lipid bilayer showed reduced conductance when treated with curcumin. Curcumin interacts with residues in the α helical N-terminus of VDAC and in the channel wall, as revealed by molecular docking, followed by mutational analysis. N-terminus mimicking peptide showed conformational changes in circular dichroism, upon curcumin treatment. We propose that the interaction of curcumin with amino acids in N-terminus and in channel wall fixes the α helix in closed conformation. This restricts its movement which is required for the opening of the channel.

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