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The mitochondrial voltage dependent channel voltage dependent anion selective channel is modified asymmetrically by succinic anhydride

, : The mitochondrial voltage dependent channel voltage dependent anion selective channel is modified asymmetrically by succinic anhydride. Journal of Membrane Biology 83(1-2): 87-94

Succinic anhydride was previously shown to react with the outer mitochondrial membrane channel-forming protein, VDAC [voltage dependent anion-selective channel], resulting in the loss of its voltage dependence. The anhydride was presently added to VDAC held in a particular conformational state by means of an applied electric field. VDAC was inserted into the membranes from the cis side and the anhydride was added either to the cis or trans side. Channels modified in the open state behaved similarly whether anhydride was added to the cis or trans side. Modifications of VDAC in either of the 2 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 the cis and trans 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.

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