Figure 3. A model depicting mitochondrial deterioration and cell death in storage diseases.

In the normal cells (left) Ca²⁺ fluxes induced by hormones and neurotransmitters (step 1) are buffered by the energized mitochondria. The Ca²⁺ dependent components of oxidative phosphorylation chain (step 2) respond by producing more ATP. The resulting spike in ATP promotes Ca²⁺ extrusion and prevents pro-apoptotic effects of Ca²⁺. In cells with lysosomal storage diseases (right), the general mitochondrial function is impaired due to buildup of dysfunctional mitochondria (step 4), resulting in the loss of Ca²⁺/ATP-driven feedback loop, which leads to pro-apoptotic effects of Ca²⁺ and cell death.