Fig. 2.

Expression of VAPB or PTPIP51 rescues mutant TDP43 induced disruption to IP3 receptor mediated delivery of Ca²⁺ to mitochondria. (a and b) SH-SY5Y cells were transfected with EGFP + control (CTRL) vector, EGFP-TDP43-Q331K or TDP43-A382T + control vector and EGFP-TDP43-Q331K/EGFP-TDP43-A382T + either VAPB or PTPIP51 as indicated. Cells were loaded with Rhod-2 AM and Ca²⁺ release induced by treatment with oxotremorine-M (OxoM). Representative Rhod-2 AM fluorescence traces are shown on the left with OxoM treatment depicted by shaded area; normalised peak values are shown in the bar charts on the right. Expression of TDP43-Q331K or TDP43-A382T reduced mitochondrial Ca²⁺ levels and this was rescued by VAPB/PTPIP51 expression. Data were analysed by one-way ANOVA with Tukey’s post hoc test. N = 62–96 cells from 3 independent experiments in (a) and N = 48–69 cells from 3 independent experiments in (b). Error bars are SEM; *** p≤0.001, ns not significant