Fig. 2.

Schematic representation illustrating the possible mechanism of involvement of intramitochondrial Ca²⁺ in epithelial apoptosis. 13-S HODE secreted from inflammatory cells including macrophages can activate TRPV1 (transient receptor potential cation channel subfamily V member 1) present in the epithelial membrane which perturbs the Ca²⁺ homeostasis, resulting in an increased intramitochondrial Ca²⁺, which can activate calpain 10. Calpain 10 releases cytochrome c from mitochondria into the cytosolic milieu. Cytochrome c then activates Caspase 3 which is involved in DNA fragmentation and eventually foments the apoptosis of epithelia. The allergen, chicken egg ovalbumin (OVA)/IL-13 may be involved in increasing intramitochondrial calcium via the MCU complex. Increased intramitochondrial Ca²⁺ is apparent in inducing ROS production and vice versa, this leads to the release of cytochrome c into the cytoplasm which further activates caspase-3. Caspase-3 can induce epithelial cell apoptosis. MCU inhibitor may inhibit epithelial apoptosis and augment the magnitude of survivability of epithelia.