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

• Published in: Biochimica et biophysica acta 2015-01, Vol.1848 (1), p.151-158
• Main Authors: Tewari, Debanjan, Ahmed, Tofayel, Chirasani, Venkat R., Singh, Pradeep K., Maji, Samir K., Senapati, Sanjib, Bera, Amal Kanti
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Binding Sites - genetics; Blotting, Western; Cattle; Circular Dichroism; Curcumin; Curcumin - chemistry; Curcumin - metabolism; Curcumin - pharmacology; Dose-Response Relationship, Drug; Gating; Humans; Ion channel; Ion Channel Gating - drug effects; Ion Channel Gating - genetics; Ion Channel Gating - physiology; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Molecular Docking Simulation; Molecular Structure; Mutation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Spectrophotometry; VDAC; Voltage-Dependent Anion Channel 1 - chemistry; Voltage-Dependent Anion Channel 1 - genetics; Voltage-Dependent Anion Channel 1 - metabolism
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2014.10.014

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. [Display omitted] •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.