Figure 4.

A Rise in [Ca²⁺]_c Induces [Ca²⁺]_m Overload and Δψm Depolarization in PINK1 KD/KO Cells

(A) Arrows mark UV-induced flash photolysis of cells loaded with Ca-NPEGTA, fluo-4, and TMRM. In (A), mouse WT neurons demonstrated an increase in [Ca²⁺]_c in response to flash photolysis, with no change in Δψm.

(B) In mouse PINK1 KO neurons, flash photolysis induced an increase in [Ca²⁺]_c with profound depolarization of the mitochondria.

(C) In the same experiment performed on human PINK1 KD neurons, the photolysis-induced rise in [Ca²⁺]_c resulted in a dramatic increase in [Ca²⁺]_m, as demonstrated by the fluo-4 signal in the mitochondrial area (Figure 4Cg). This was rapidly followed by mitochondrial depolarization and subsequent release of fluo-4 from the mitochondrial area.

(D) Application of 10 μm CGP-37157 to control neurons induced the same [Ca²⁺]_m overload and Δψm depolarization seen in PINK1 KD.