Protection against Mitochondrial and Metal Toxicity Depends on Functional Lipid Binding Sites in ATP13A2

Figure 5

The capacity of ATP13A2 to interact with PA/PI(3,5)P2 is essential to protect against heavy metal-induced cytotoxicity. SHSY5Y cell lines stably overexpressing FLUC, ATP13A2 shRNA, ATP13A2 WT, and LBS1–3 mutants were exposed to toxic heavy metal concentrations of Zn²⁺ (150 μM ((a) and (b))) or Mn²⁺ (2 μM ((c) and (d))). Cell death induction was assessed by propidium iodide (PI ) based flow cytometry ((a) and (c)) and cell viability by MUH assay ((b) and (d)). Data are the mean of 3 independent experiments ± SD. statistical differences between FLUC and WT-OE/sh-ATP13A2/LBS1/LBS2/LBS3/LBS1.2.3 (1 mark, ; 2 marks, ; 3 marks, ) (ANOVA with Bonferroni post hoc test).

(a)

(b)

(c)

(d)