Abstract:
:Reversible blockage of the voltage-dependent anion channel (VDAC) of the mitochondrial outer membrane by dimeric tubulin is being recognized as a potent regulator of mitochondrial respiration. The tubulin-blocked state of VDAC is impermeant for ATP but only partially closed for small ions. This residual conductance allows studying the nature of the tubulin-blocked state in single-channel reconstitution experiments. Here we probe this state by changing lipid bilayer charge from positive to neutral to negative. We find that voltage sensitivity of the tubulin-VDAC blockage practically does not depend on the lipid charge and salt concentration with the effective gating charge staying within the range of 10-14 elementary charges. At physiologically relevant low salt concentrations, the conductance of the tubulin-blocked state is decreased by positive and increased by negative charge of the lipids, whereas the conductance of the open channel is much less sensitive to this parameter. Such a behavior supports the model in which tubulin's negatively charged tail enters the VDAC pore, inverting its anionic selectivity to cationic and increasing proximity of ion pathways to the nearest lipid charges as compared with the open state of the channel.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Gurnev PA,Queralt-Martin M,Aguilella VM,Rostovtseva TK,Bezrukov SMdoi
10.1016/j.bpj.2012.03.058subject
Has Abstractpub_date
2012-05-02 00:00:00pages
2070-6issue
9eissn
0006-3495issn
1542-0086pii
S0006-3495(12)00399-2journal_volume
102pub_type
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