Origami in the outer membrane: the transmembrane arrangement of mitochondrial porins

Biochem Cell Biol. 2002;80(5):551-62. doi: 10.1139/o02-149.


Voltage-dependent anion-selective channels (VDAC), also known as mitochondrial porins, are key regulators of metabolite flow across the mitochondrial outer membrane. Porins from a wide variety of organisms share remarkably similar electrophysiological properties, in spite of considerable sequence dissimilarity, indicating that they share a common structure. Based on primary sequence considerations, analogy with bacterial porins, and circular dichroism analysis, it is agreed that VDAC spans the outer membrane as a beta-barrel. However, the residues that form the antiparallel beta-strands comprising this barrel remain unknown. Various predictive methods, largely based on the known structures of bacterial beta-barrels, have been applied to the primary sequences of VDAC. Refinement and confirmation of these predictions have developed through numerous investigations of wild-type and variant porins, both in mitochondria and in artificial membranes. These experiments have involved VDAC from several sources, precluding the generation of a unified model. Herein, using the Neurospora VDAC sequence as a template, the published structural information and predictions have been reassessed to delineate a model that satisfies most of the available data.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane / metabolism*
  • Circular Dichroism
  • Forecasting
  • Humans
  • Ion Channel Gating / physiology*
  • Ion Channels / chemistry*
  • Ion Channels / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology
  • Mitochondria / physiology*
  • Models, Molecular
  • Molecular Sequence Data
  • Porins / chemistry*
  • Porins / physiology*
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Voltage-Dependent Anion Channels


  • Ion Channels
  • Membrane Proteins
  • Porins
  • Voltage-Dependent Anion Channels