title: VDAC channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function.
abstract: The mitochondrial channel, VDAC, forms large (3 nm in diameter) aqueous pores through membranes. We measured ATP flow (using the luciferin/luciferase method) through these channels after reconstitution into planar phospholipid membranes. In the open state of VDAC, as many as 2 x 10(6) ATP molecules can flow through one channel per second. The half-maximum rate occurs at approximately 75 mM ATP. The permeability of a single channel for ATP is 1.1 x 10(-14) cm3/s (about 1 cm/s after correcting for cross-sectional area), which is 100 times less than the permeability for chloride and 10 times less than that for succinate. Channel closure results in a 50% reduction in conductance, showing that monovalent ions are still quite permeable, yet ATP flux is almost totally blocked. This is consistent with an electrostatic barrier that results in inversion of the selectivity of the channel and could be an example of how large channels selectively control the flow of charged metabolites. Thus VDAC is ideally suited to controlling the flow of ATP between the cytosol and the mitochondrial spaces.
authors.affiliation: Department of Zoology, University of Maryland, College Park 20742, USA.
authors.forename: T
authors.initials: T
authors.lastname: Rostovtseva
authors.forename: M
authors.initials: M
authors.lastname: Colombini
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis* / Q000378:metabolism*; D055592:Biophysical Phenomena; D001703:Biophysics; D002463:Cell Membrane Permeability; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D018272:Porins; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D018272:Porins; D050994:Voltage-Dependent Anion Channels; D000255:Adenosine Triphosphate