Figure 1. Model for membrane stretch activation of Piezo1/TRPV4 and calcium-signaling pathways.

(A) Following membrane deformity (e.g., stretch), Piezo1 is activated, causing a transient increase in cytosolic calcium as well as increased PLA2 activity. PLA metabolites then activate TRPV4, which opens to let calcium enter and ultimately depolarize the mitochondria (1). The two transporters can be activated by multiple stimuli. (B) Multiple calcium transporters can affect signaling and lead to mitochondrial depolarization and trigger inflammatory responses through NF-κB activation and mitochondrial injury. Whether RyRs are present at ER-mitochondrial contacts in acinar cells is unknown.