Structure and Function of the VDAC Ion Channel

  • Marco Colombini
Part of the NATO ASI Series book series (volume 83)


Mitochondria function within the cytoplasm of eukaryotic cells separated from the cytoplasm by a membranous barrier, the mitochondrial outer membrane. Permeability pathways in this membrane, such as the VDAC channels, can be viewed both as a means by which metabolites may travel from one compartment to the other and as a means of controlling the flux of such metabolites. Both of these functions depend on the properties of the permeating pathways, such as the VDAC channels. By examining in detail the properties of VDAC one should obtain insights into its role in mitochondrial function.


Outer Membrane Cylindrical Shell Closed State Voltage Dependence Mitochondrial Outer Membrane 
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  1. Benz R, Kottke M, Brdiczka D (1990) The cationically selective state of the mitochondrial outer membrane pore: a study with intact mitochondria and reconstituted mitochondrial porin. Biochim Biophys Acta 1022: 311–318.PubMedCrossRefGoogle Scholar
  2. Benz R, Wojtczak L, Bosch W, Brdiczka D (1988) Inhibition of adenine nucleotide transport through the mitochondrial porin by a synthetic polyanion. FEBS Lett 231: 75–80PubMedCrossRefGoogle Scholar
  3. Blachly-Dyson E, Peng SZ, Colombini M, Forte M (1989) Probing the structure of the mitochondrial channel, VDAC, by site-directed mutagenesis: a progress report. J Bioenerg Biomembr 21: 471–483PubMedCrossRefGoogle Scholar
  4. Blachly-Dyson E, Peng SZ, Colombini M, Forte M (1990) Alteration of the selectivity of the VDAC ion channel by site-directed mutagenesis: implications for the structure of a membrane ion channel. Science 247: 1233–1236PubMedCrossRefGoogle Scholar
  5. Blachly-Dyson E, Zambrowicz EB, Yu WH, Adams V, McCabe ERB, Adelman J, Colombini M, Forte M (1993) Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel. J Biol Chem 268: 1835–1841PubMedGoogle Scholar
  6. Colombini M (1980b) Structure and mode of action of a voltage-dependent anion-selective channel (VDAC) located in the outer mitochondrial membrane. Ann NY Acad Sci 341: 552–563PubMedCrossRefGoogle Scholar
  7. Colombini M (1986) Voltage gating in VDAC: toward a molecular mechanism. In “Ion Channel Reconstitution” (C. Miller, ed.), pp. 533–552, Plenum, New York.Google Scholar
  8. Colombini M (1989) Voltage gating in the mitochondrial channel, VDAC. J Membr Biol 111: 103–111PubMedCrossRefGoogle Scholar
  9. Colombini M, Yeung CL, Tung J, König T (1987) The mitochondrial outer membrane channel, VDAC, is regulated by a synthetic polyanion. Biochim Biophys Acta 905: 279–286PubMedCrossRefGoogle Scholar
  10. Gellerich FN, Kunz W (1987) Cause and consequences od dynamic compartmentation of adenine nucleotides in the mitochondrial intermembrane space in respect to exchange of energy rich phosphates between cytosol and mitochondria. Biomed Biochim Acta 46: S545–S548PubMedGoogle Scholar
  11. Holden MJ, Colombini M (1988) The mitochondrial outer membrane channel, VDAC, is modulated by a soluble protein. FEBS Lett 241: 105–109PubMedCrossRefGoogle Scholar
  12. Liu M, Colombini M (1991) Voltage gating in the mitochondrial outer membrane channel, VDAC, is regulated by a very conserved protein. Am J Physiol 260: C371–C374PubMedGoogle Scholar
  13. Liu M, Colombini M (1992a) Regulation of mitochondrial respiration by controlling the permeability of the outer membrane through the mitochondrial channel, VDAC. Biochim Biophys Acta 1098: 255–260PubMedCrossRefGoogle Scholar
  14. Liu MY, Colombini M (1992b) A soluble protein increases the voltage dependence of the mitochondrial channel, VDAC. J Bioenerg Biomembr 24: 41–46PubMedCrossRefGoogle Scholar
  15. Mannella CA, Gou XW (1990) Interaction between the VDAC channel and a polyanionic effector. Biophys J 57: 23–31PubMedCrossRefGoogle Scholar
  16. Mannella CA, Forte M, Colombini M (1992) Toward the molecular structure of the mitochondrial channel, VDAC. J Bioenerg Biomembr 24: 7–19PubMedCrossRefGoogle Scholar
  17. Parsons DF, Bonner WD Jr., Verboon JG (1965) Electron microscopy of isolated plant mitochondria and plastids using both the thin-section and negative-staining techniques. Can J Bot 43: 647–655CrossRefGoogle Scholar
  18. Peng S, Blachly-Dyson E, Forte M, Colombini M (1992a) Determination of the number of polypeptide subunits in a functional VDAC channel from Saccharomyces cerevisiae. J Bioenerg Biomembr 24: 27–31PubMedCrossRefGoogle Scholar
  19. Peng S, Blachly-Dyson E, Forte M, Colombini M (1992b) Large scale rearrangement of protein domains is associated with voltage gating of the VDAC channel. Biophys J 62: 123–135PubMedCrossRefGoogle Scholar
  20. Schein SJ, Colombini M, Finkelstein A (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from Paramecium mitochondria. J Membr Biol 30: 99–120PubMedCrossRefGoogle Scholar
  21. Teorell T (1957) Transport processes and electrical phenomena in ionic membranes. Prog Biophys Chem 3: 305–369Google Scholar
  22. Thomas L, Kocsis E, Colombini M, Erbe E, Trus BL, Steven AC (1991) Surface topography and molecular stoichiometry of the mitochondrial channel, VDAC, in crystalline arrays. J Struct Biol 106: 161–171PubMedCrossRefGoogle Scholar
  23. Thomas L, Blachly-Dyson E, Colombini M, Forte M (1993) Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel. Proc. Natl. Acad. USA 90: 5446–5449CrossRefGoogle Scholar
  24. Werkheiser WC, Bartley W (1957) The study of steady-state concentrations of internal solute of mitochondria by rapid centrifugal transfer to fixation medium. Biochem J 66: 79–91PubMedGoogle Scholar
  25. Wojtczak L, Zaluska H (1969) On the impermeability of the outer mitochondrial membrane to cytochrome c. I. Studies on whole mitochondria. Biochim Biophys Acta 193: 64–72PubMedCrossRefGoogle Scholar
  26. Wunder UR, Colombini M (1991) Patch clamping VDAC in liposomes containing whole mitochondrial membranes. J Membr Biol 123: 83–91PubMedCrossRefGoogle Scholar
  27. Zambrowicz EB, Colombini M (1993) Zero-current potentials in a large membrane channel: a simple theory accounts for complex behavior. Biophys J (in press)Google Scholar
  28. Zhang DW, Colombini M (1990) Group IIIA-metal hydroxides indirectly neutralize the voltage sensor of the voltage-dependent mitochondrial channel, VDAC, by interacting with a dynamic binding site. Biochim Biophys Acta 1025: 127–134CrossRefGoogle Scholar
  29. Zalman LS, Nikaido, H, Kagawa, Y (1980) Mitochondrial outer membrane contains a protein producing nonspecific diffusion channels. J Biol Chem 255: 1771–1774Google Scholar
  30. Zimmerberg J, Parsegian VA (1986) Polymer inaccessible volume changes during opening and closing of a voltage-dependent ionic channel. Nature (Lond.) 323: 36–39CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Marco Colombini
    • 1
  1. 1.Department of ZoologyUniversity of MarylandCollege ParkUSA

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