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Biophys. J. BioFAST: First Published September 30, 2005. doi:10.1529/biophysj.105.070037
© 2005 by the Biophysical Society.

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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

New Insights into the Mechanism of Permeation through Large Channels

Alexander G Komarov 1, Defeng Deng 2, William J Craigen 2 and Marco Colombini 3*

1 University of Maryland
2 Depts of Mol and Human Genetics and Pediatrics, Baylor Col of Med
3 Univ. of Maryland

* To whom correspondence should be addressed. E-mail: colombin{at}umd.edu.

Submitted on July 5, 2005
Revised on August 15, 2005
Accepted on 8 September 2005


  Abstract
The mitochondrial channel, VDAC, regulates metabolite flux across the outer membrane. The open conformation has a higher conductance and anionic selectivity, while closed states prefer cations and exclude metabolites. In this study 5 mutations were introduced into mouse VDAC2 to neutralize the voltage sensor. Inserted into planar membranes, mutant channels lack voltage gating, have a lower conductance, demonstrate cationic selectivity and, surprisingly, are still permeable to ATP. The estimated ATP flux through the mutant is comparable to that for wild-type VDAC2. The outer membranes of mitochondria containing the mutant are permeable to NADH and ADP/ATP. Both experiments support the counterintuitive conclusion that converting a channel from an anionic to a cationic preference does not substantially influence the flux of negatively charged metabolites. This finding supports our previous proposal that ATP translocation through VDAC is facilitated by a set of specific interactions between ATP and the channel wall.

Key Words: VDAC, channel properties, mitochondria, mutant, planar membranes, selectivity




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Copyright © 2005 by the Biophysical Society.