Mouse VDAC isoforms expressed in yeast: channel properties and their roles in mitochondrial outer membrane permeability

J Membr Biol. 1999 Jul 15;170(2):89-102. doi: 10.1007/s002329900540.


The channel-forming protein called VDAC forms the major pathway in the mitochondrial outer membrane and controls metabolite flux across that membrane. The different VDAC isoforms of a species may play different roles in the regulation of mitochondrial functions. The mouse has three VDAC isoforms (VDAC1, VDAC2 and VDAC3). These proteins and different versions of VDAC3 were expressed in yeast cells (S. cerevisiae) missing the major yeast VDAC gene and studied using different approaches. When reconstituted into liposomes, each isoform induced a permeability in the liposomes with a similar molecular weight cutoff (between 3,400 and 6,800 daltons based on permeability to polyethylene glycol). In contrast, electrophysiological studies on purified proteins showed very different channel properties. VDAC1 is the prototypic version whose properties are highly conserved among other species. VDAC2 also has normal gating activity but may exist in 2 forms, one with a lower conductance and selectivity. VDAC3 can also form channels in planar phospholipid membranes. It does not insert readily into membranes and generally does not gate well even at high membrane potentials (up to 80 mV). Isolated mitochondria exhibit large differences in their outer membrane permeability to NADH depending on which of the mouse VDAC proteins was expressed. These differences in permeability could not simply be attributed to different amounts of each protein present in the isolated mitochondria. The roles of these different VDAC proteins are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Electrophysiology
  • Gene Expression
  • Intracellular Membranes / metabolism
  • Ion Channel Gating / physiology
  • Ion Channels / physiology
  • Lipid Bilayers / metabolism
  • Liposomes / metabolism
  • Mice
  • Mitochondria / physiology
  • Mitochondria / ultrastructure
  • NAD / physiology
  • Oxidation-Reduction / drug effects
  • Permeability / drug effects
  • Porins / genetics
  • Porins / pharmacology*
  • Porins / physiology
  • Protein Isoforms / pharmacology
  • Protein Isoforms / physiology
  • Voltage-Dependent Anion Channel 1
  • Voltage-Dependent Anion Channel 2
  • Voltage-Dependent Anion Channels
  • Yeasts / genetics


  • Ion Channels
  • Lipid Bilayers
  • Liposomes
  • Porins
  • Protein Isoforms
  • Vdac1 protein, mouse
  • Vdac2 protein, mouse
  • Voltage-Dependent Anion Channel 2
  • Voltage-Dependent Anion Channels
  • NAD
  • Voltage-Dependent Anion Channel 1