Wedeloside, a powerful inhibitor and ligand of the mitochondrial ADP/ATP carrier

The effect of wedeloside, an atractyloside analogue occurring in the Australian weed Wedelia asperrima, on the ADP/ATP carrier is investigated on 3 levels; the ADP stimulated respiration, the ADP/ATP exchange, and the binding in competition with atractylate (ATR) and carboxyatractylate (CAT). The inhibition of respiration and of ADP/ATP exchange by wedeloside is nearly uncompetitive with ADP. The competitive binding with [3H]cat and [3H]ATR reveals a high binding affinity of wedeloside similar to that of CAT. The titration of the ADP/ATP exchange and of the binding with wedeloside gives a titer of 0.35 μmolg protein for rat liver protein and the titer of the binding gives 2.7 μmolg protein for beef heart mitochondria. The 1.8-times higher titers than with CAT may indicate that two molecules of wedeloside bind to one ADP/ATP carrier dimer in contrast to the half site reactivity known for the binding of the other ligands.