FIGURE 2: Heme is a major ART-reactive agent inside cells. (A) Heme knockdown significantly suppresses the rate of ART metabolism in yeast. Shown is a HPLC analysis of ART after incubation with growing yeast cultures. Heme knockdown (HEM2 KD) reduces the rate of ART consumption. (B) Heme knockdown dramatically increases, instead of decreases, the potency of ART in inhibiting mitochondrial actions (so that the yeast growth on non-fermentable media is restricted). When heme level is reduced, ART inhibition of yeast can be observed in 50 nM on the non-fermentable agar plate. Part of this figure is adapted from reference [47].

47. Sun C, Li J, Cao Y, Long G, Zhou B (2015). Two distinct and competitive pathways confer the cellcidal actions of artemisinins. Microb Cell 2(1): 14-25.