FIGURE 8. Model of the events sequence induced in L. mexicana promastigotes after addition of Erg-GTr or Erg-GTr₂.

When promastigotes are treated with ergosterone-triazol coupled molecules, a rapid increase in the cytoplasmic Ca²⁺ level, which mainly comes from acidocalcisomes, is induced. This divalent cation should activate signal cascades that trigger some of the phenotypes observed as PS exposure, ↑ΔΨ_mit, and autophagy exacerbation. Intracellular ROS increase is also one of the earliest events found after Erg-GTr or Erg-GTr₂ addition. Hyperpolarized mitochondrion may originate large amounts of ROS. This effector can induce DNA damage, among others, which may conduce to cell cycle arrest. Finally, autophagy could also be directly induced by the effect of ergosterone-triazol coupled molecules on cell membranes, which has been widely reported in the literature to be caused by azoles. Abbreviations used: acidocalcisomes (A); autophagy vacuoles (AF); lysosomes (L); nucleus (N); kinetoplast (K); mitochondrion (M).