Fig. 5.

Propofol affect cell survival in a dose- and lysosome H⁺ homeostasis dependent manner via activation of InsP₃Rs and/or RYRs. Propofol at clinically relevant concentrations (1–20 μΜ, left side) adequately activate InsP₃R and/or RYR, supporting normal lysosome H⁺/Ca²⁺ homeostasis and cell survival. However, excessive activation of InsP₃Rs and/or RYRs by propofol at pharmacological concentrations (>50 μΜ, right side) and associated depletion of ER Ca²⁺ together with abnormal elevation of cytosolic Ca²⁺ concentration ([Ca²⁺ ]_c) resulted in the disruption of lysosome H⁺/Ca²⁺ homeostasis, and impairment of endosome-lysosome fusion and autophagic dysfunction, eventually leading to cell death.