Figure 8. Model of T. cruzi necrotic cell death.

The cellular events during the necrotic death of epimastigotes were reconstructed from the results of this and published studies. The events occur in the following order: 1: cytoplasmic calcium overload from acidocalcisomes and/or the ER (red dots represent Ca²⁺); 2: accumulation of Ca²⁺ in the mitochondria, leading to inner membrane depolarization (↓Ψm) and ROS (reactive oxygen species) production; 3: RMP, due to the action of ROS and/or Ca²⁺- activated calpains, potentially corresponding to the point of no return in the necrotic pathway; 4: extensive cell degradation by proteases released from the reservosomes; 5: cell lysis. N: nucleus, ER: endoplasmic reticulum, M: mitochondria, K: kinetoplast, R: reservosome; A: acidocalcisome.