Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes

The induction of the formation of inclusion vesicles in Leishmania amazonen sis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafin e has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energ y loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demon strated. Endoplasmic reticulum cisternae formed membrane whorls which enclo sed large portions of the cytoplasm and sometimes circumscribed acidocalcis omes. In addition, acid phosphatase activity, as well as the endocytic trac ers horseradish peroxidase and gold-labelled transferrin and cystatin C wer e detected within these organelles in both SBI-treated and untreated parasi tes. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes .