VDAC channels differentiate between natural metabolites and synthetic molecules

VDAC provides the major permeability pathway through the mitochondrial outer membrane by forming voltage-gated channels with pore radius of 1.2-1.5 nm. We find that VDAC can select among comparably-charged molecules with a much smaller effective radius, 0.4-0.5 nm. The molecules studied were the nuc...

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Bibliographic Details
Published in:The Journal of membrane biology 2002-05, Vol.187 (2), p.147-156
Main Authors: Rostovtseva, T K, Komarov, A, Bezrukov, S M, Colombini, M
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - chemistry
Arylsulfonates - chemistry
Electrochemistry - methods
Glutamates - chemistry
Ion Channel Gating
Ion Channels - chemistry
Membranes, Artificial
Models, Molecular
NAD - chemistry
Neurospora crassa - metabolism
Porins - chemistry
Porins - isolation & purification
Sensitivity and Specificity
Structure-Activity Relationship
Uridine Triphosphate - chemistry
Voltage-Dependent Anion Channels
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Summary:VDAC provides the major permeability pathway through the mitochondrial outer membrane by forming voltage-gated channels with pore radius of 1.2-1.5 nm. We find that VDAC can select among comparably-charged molecules with a much smaller effective radius, 0.4-0.5 nm. The molecules studied were the nucleotides, ATP, UTP, NADH and synthetic anions, tetraglutamate (T-Glu) and 1-hydroxypyrene-3,6,8-trisulfonate (HPTS). VDAC channels were reconstituted into planar phospholipid membranes bathed in 1.0 M NaCl (buffered to pH 8.0). The nucleotides decreased the conductance of VDAC for NaCl demonstrating that they could permeate into the channel. In contrast, T-Glu and HPTS did not change the single-channel conductance, indicating exclusion from the channel. Reversal potential measurements report near ideal selectivity of Na + over T-Glu. The nucleotides increased single-channel noise as they penetrated into the channel, while T-Glu had no effect. HPTS increased noise, but unlike NADH, this was not voltage-dependent when HPTS was added asymmetrically, indicating no penetration into the channel. The differences in effective size and charge cannot explain the difference in permeation characteristics. Thus VDAC must select among these based on shape and charge distribution. We propose that the electrostatic environment within the channel has been evolutionarily selected to favor the passage of adenine nucleotides.
ISSN:0022-2631
1432-1424
DOI:10.1007/s00232-001-0159-1