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

Debanjan Tewari; Tofayel Ahmed; Venkat R Chirasani; Pradeep K Singh; Samir K Maji; Sanjib Senapati; Amal Kanti Bera

doi:10.1016/j.bbamem.2014.10.014

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

Biochim Biophys Acta. 2015 Jan;1848(1 Pt A):151-8. doi: 10.1016/j.bbamem.2014.10.014. Epub 2014 Oct 23.

Authors

Debanjan Tewari¹, Tofayel Ahmed¹, Venkat R Chirasani¹, Pradeep K Singh², Samir K Maji², Sanjib Senapati¹, Amal Kanti Bera³

Affiliations

¹ Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
² Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
³ Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India. Electronic address: amal@iitm.ac.in.

PMID: 25459681
DOI: 10.1016/j.bbamem.2014.10.014

Abstract

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.

Keywords: Apoptosis; Curcumin; Gating; Ion channel; Mitochondria; VDAC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites / genetics
Blotting, Western
Cattle
Circular Dichroism
Curcumin / chemistry
Curcumin / metabolism
Curcumin / pharmacology*
Dose-Response Relationship, Drug
Humans
Ion Channel Gating / drug effects
Ion Channel Gating / genetics
Ion Channel Gating / physiology
Lipid Bilayers / chemistry
Lipid Bilayers / metabolism
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
Voltage-Dependent Anion Channel 1 / chemistry*
Voltage-Dependent Anion Channel 1 / genetics
Voltage-Dependent Anion Channel 1 / metabolism

Substances

Lipid Bilayers
Mitochondrial Proteins
VDAC1 protein, human
Voltage-Dependent Anion Channel 1
Curcumin