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

Debanjan Tewari1, Tofayel Ahmed1, Venkat R Chirasani1

  • 1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.

Insights

Curcumin reduces mitochondrial VDAC-1 channel conductance by binding to its N-terminus and channel wall. This interaction stabilizes the channel in a closed conformation, inhibiting its function in apoptosis.

Area of Science:

  • Mitochondrial biology
  • Biophysics
  • Molecular pharmacology

Background:

  • Voltage-dependent anion channel (VDAC) is critical for mitochondrial function and apoptosis.
  • Curcumin, a natural compound, has shown potential in modulating cellular processes.

Purpose of the Study:

  • To investigate the effect of curcumin on human VDAC-1 channel activity.
  • To elucidate the molecular mechanism of curcumin interaction with VDAC-1.

Main Methods:

  • Reconstitution of human VDAC-1 in planar lipid bilayers.
  • Electrophysiological measurements of channel conductance.
  • Molecular docking simulations.
  • Site-directed mutagenesis.
  • Circular dichroism spectroscopy of VDAC-1 N-terminus peptide.

Main Results:

  • Curcumin treatment significantly reduced the conductance of VDAC-1 reconstituted in lipid bilayers.
  • Molecular docking and mutational analysis identified curcumin binding sites in the VDAC-1 N-terminus and channel wall.
  • Circular dichroism revealed conformational changes in the VDAC-1 N-terminus peptide upon curcumin exposure.
  • These findings suggest curcumin stabilizes VDAC-1 in a closed conformation.

Conclusions:

  • Curcumin directly interacts with human VDAC-1, inhibiting its channel activity.
  • The interaction involves the N-terminus and channel wall, leading to a closed channel conformation.
  • This mechanism provides insight into curcumin's role in regulating mitochondrial function and apoptosis.

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