Human VDAC isoforms differ in their capability to interact with minocycline and to contribute to its cytoprotective activity

Mitochondrion. 2016 May:28:38-48. doi: 10.1016/j.mito.2016.03.004. Epub 2016 Mar 16.

Abstract

It has been previously demonstrated that cytoprotective activity displayed by minocycline in the case of the yeast Saccharomyces cerevisiae cells pretreated with H2O2 requires the presence of functional VDAC (YVDAC1). Thus, we decided to transform YVDAC1-depleted yeast cells (Δpor1 cells) with plasmids expressing human VDAC isoforms (HVDAC1, HVDAC2, HVDAC3) to estimate their involvement in the minocycline cytoprotective effect. We observed that only expression of HVDAC3 in Δpor1 cells provided minocycline-mediated cytoprotection against H2O2 although all human isoforms are functional in Δpor1 cells. The observation appears to be important for on-going discussion concerning VDAC isoform roles in mitochondria and cell functioning.

Keywords: Channel activity of human VDAC3; Cytoprotection; Human VDAC isoforms; Minocycline; The yeast Sacharomyces cerevisiae.

MeSH terms

  • Antioxidants / metabolism*
  • Antioxidants / pharmacology*
  • Cytoprotection*
  • Humans
  • Hydrogen Peroxide / toxicity
  • Minocycline / metabolism*
  • Minocycline / pharmacology*
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Voltage-Dependent Anion Channels / genetics
  • Voltage-Dependent Anion Channels / metabolism*

Substances

  • Antioxidants
  • Protein Isoforms
  • Recombinant Proteins
  • Voltage-Dependent Anion Channels
  • Hydrogen Peroxide
  • Minocycline