ANION CHANNELS IN THE MITOCHONDRIAL OUTER-MEMBRANE

At the beginning phase, the reconstitution of an anion-selective channel, from mitochondria, came as a surprise. The existence of large channels in the outer membrane, favoring anions, fits nicely with the major function of mitochondria, energy transduction. Substrates and products are mostly negatively charged molecules, such as pyruvate, adenosine diphosphate (ADP), adenosine triphosphate (ATP), phosphate, etc. The reconstitution into planar phospholipid membranes of large voltage gated channels, called VDAC (voltage-dependent anion-selective channel), indicated that these channels are not static structures but dynamic and under regulation. VDAC channels form extremely conductive pathways in phospholipid membranes. Such channels are the primary pathway for the flow of metabolites across the mitochondrial outer membrane. Their well-conserved properties include a variety of regulatory mechanisms that could restrict the flow of metabolites between the cytoplasm and the mitochondrion. Such a bottleneck could limit such things, as energy production and mitochondrial growth and reproduction. Thus, VDAC may play an important role in these and other processes. The importance of VDAC and its properties to mitochondrial function is strongly indicated by the remarkable conservation of its structure and functional properties. Discovery of new regulatory mechanisms and their remarkable conservation provides further evidence for an important and elaborate regulatory system. © 1994, Academic Press, Inc. All rights reserved.