Probing the Voltage Gating and Modulation of a Voltage Dependent Channel

摘要

VDAC channels form aqueous pathways through the mitochondrial outer membrane. These channels are formed by 3OkDa protein monomers. The channels are selective for anions and will allow a variety of metabolites including ATP to cross the membrane. The channel structure is mostly formed by a beta barrel and consists of 1 alpha helix and 13 beta strands. Channel gating results in channels that have a lower overall conductance but inverted selectivity so that ATP and many anionic metabolites have drastically reduced permeability. There are 2 fundamental gating processes, one functioning at positive and the other at negative potentials. Voltage gating results from the movement of a large domain of net positive charge out from within the membrane to the membrane surface. A variety of agents, including NADH and intermembrane-space proteins, modulate the properties of VDAC, usually favoring channel closure. These agents are believed to be part of a complex regulatory system that controls mitochondrial function.