FUNCTIONAL DIFFERENCES AMONG WHEAT VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) ISOFORMS EXPRESSED IN YEAST - INDICATION FOR THE PRESENCE OF A NOVEL VDAC-MODULATING PROTEIN

VDAC is a voltage gated anion channel located in the mitochondrial out er membrane, presumably participating in controlling aerobic metabolis m, Three distinct wheat vdac cDNAs were expressed in a vdac minus yeas t strain and successfully complemented its defective phenotype, The gr owth curves of these transformants were different. The wheat channel i soforms were functionally characterized following purification from ye ast mitochondria and reconstitution into soybean phospholipid planar m embranes, All three isoforms yielded voltage-dependent anion channels with electrophysiological parameters comparable to known VDACs. Isofor m-related functional features (specific conductance levels, kinetics, and gating behaviors) are reported for the first time in VDACs. The pr esence (or absence) of protease inhibitors during the purification pro cedure, and the use of Pronase on reconstituted channels, strongly sug gest that some of the unique wheat VDAC properties are due to co-purif ication of a yeast channel-modulating protein, Its effects, different from the reported functional interactions of the channel with hexo- or creatine kinases, could not be mimicked by the protein termed VDAC mo dulator, indicating the presence of a novel VDAC modulator, In additio n to strengthening VDAC presumed role in metabolism, the functional di versity of the channels (as shown here in two different systems) impli es a highly dynamic outer membrane permeability. Our results are consi stent with VDAC functioning as a heteromer including one pore protein and other modulating subunits.