The Journal of Membrane Biology

, Volume 83, Issue 1–2, pp 87–94 | Cite as

The mitochondrial voltage-dependent channel, VDAC, is modified asymmetrically by succinic anhydride

  • Charles Doring
  • Marco Colombini


In the accompanying paper, succinic anhydride was shown to react with the outer mitochondrial membrane channel-forming protein, VDAC, resulting in the loss of its voltage dependence. In this paper, the anhydride was added to VDAC held in a particular conformational state by means of an applied electric field. VDAC was inserted into the membranes from thecis side and the anhydride was added either to thecis ortrans side. Channels modified in the open state behaved similarly whether anhydride was added to thecis ortrans side. Modifications of VDAC in either of the two closed states did not. Modifications resulting in the loss of voltage-dependence occurred primarily when anhydride was added to the negative side of the membrane irrespective of which closed state the VDAC was in indicating that the accessibility of the gating charges alternated between thecis andtrans sides as the channel's conformation was changed from one closed state to the other. Despite the pronounced asymmetry, in general the resulting channels behaved in the same way in response to either positive or negative fields. A model consistent with the results is presented which proposes that the same gating charges are responsible for channel closure at both positive and negative fields.

Key Words

voltage-gating protein modification mechanism planar lipid membrane outer membrane ion transport 


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  1. Colombini, M. 1979. A candidate for the permeabiliy pathway of the outer mitochondrial membrane.Nature (London) 279:643–645Google Scholar
  2. Colombini, M. 1980a. Structure and mode of action of a voltage-dependent anion-selective channel (VDAC) located in the outer mitochondrial membrane.Ann. N.Y. Acad. Sci. 341:552–563PubMedGoogle Scholar
  3. Colombini, M. 1980b. Pore size and properties of channels from mitochondria isolated fromNeurospora crassa.J. Membrane Biol. 53:79–84Google Scholar
  4. Colombini, M. 1983. Purification of VDAC (voltage-dependent anion-selective channel) from rat liver mitochondria.J. Membrane Biol. 74:115–121Google Scholar
  5. Colombini, M. 1984. A novel mechanism for voltage control of channel conductance.J. Theor. Biol. (in press) Google Scholar
  6. Doring, C., Colombini, M. 1984. On the nature of the molecular mechanism underlying the voltage dependence of the channel-forming protein, VDAC.Biophys. J. 45:44–46Google Scholar
  7. Freitag, H., Neupert, W., Benz, R. 1982. Purification and characterization of a pore protein of the outer mitochondrial membrane fromNeurospora crassa.Eur. J. Biochem. 123:629–636PubMedGoogle Scholar
  8. Linden, M., Gellerfors, P., Nelson, B.D. 1982. Purification of a protein having pore forming activity from the rat liver mitochondrial outer membrane.Biochem. J. 208:77–82PubMedGoogle Scholar
  9. Mannella, C.A., Bonner, W.D., Jr. 1975. X-ray diffraction from oriented outer mitochondrial membranes.Biochim. Biophys. Acta 413:226–233PubMedGoogle Scholar
  10. Montal, M., Mueller, P. 1972. Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties.Proc. Natl. Acad. Sci. USA 69:3561–3566PubMedGoogle Scholar
  11. Parsons, D.F., Williams, G.R., Chance, B. 1966. Characteristics of isolated and purified preparations of the outer and inner membranes of mitochondria.Ann. N.Y. Acad. Sci. 137:643–666PubMedGoogle Scholar
  12. Roos, N., Benz, R., Brdiczka, D. 1982. Identification and characterization of the pore-forming protein in the outer membrane of rat liver mitochondria.Biochim. Biophys. Acta 686:204–214PubMedGoogle Scholar
  13. Schein, S.J., Colombini, M., Finkelstein, A. 1976. Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained fromParamecium mitochondria.J. Membrane Biol. 30:99–120Google Scholar
  14. Zalman, L.S., Nikaido, H., Kagawa, Y. 1980. Mitochondrial outer membrane contains a protein producing nonspecific diffusion channels.J. Biol. Chem. 255:1771–1774PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Charles Doring
    • 1
  • Marco Colombini
    • 1
  1. 1.Laboratories of Cell Biology, Department of ZoologyUniversity of MarylandCollege Park

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