Acidocalcisome is required for autophagy in <i>Trypanosoma brucei</i>

Lysosomes play important roles in autophagy, not only in autophagosome degradation, but also in autophagy initiation. In <i>Trypanosoma brucei,</i> an early divergent protozoan parasite<i>,</i> we discovered a previously unappreciated function of the acidocalcisome, a lysosome-related organelle characterized by acidic pH and large content of Ca²⁺ and polyphosphates, in autophagy regulation. Starvation- and chemical-induced autophagy is accompanied with acidocalcisome acidification, and blocking the acidification completely inhibits autophagosome formation. Blocking acidocalcisome biogenesis by depleting the adaptor protein-3 complex, which does not affect lysosome biogenesis or function, also inhibits autophagy. Overall, our results support the role of the acidocalcisome, a conserved organelle from bacteria to human, as a relevant regulator in autophagy.