FIGURE 6: A model for the two distinct pathways of ARTs’ actions.

ARTs act in two distinct ways: the heme pathway and the mitochondrial pathway. ARTs can be consumed by intracellular heme, inducing general damages (in the case of DHA) or tolerated/wasted (ART). ARTs can also be activated by the mitochondrial pathway, causing mitochondrial dysfunction. The heme pathway is a much less efficient pathway for killing and explains the action in some tumor cells and probably other general cell types. The much more potent mitochondrial pathway is shared by ARTs, and can explain the action of ARTs on malaria parasites and yeast grown on nonfermentable media.