Fig. 3.

In the absence of MCU, mitochondrial Ca²⁺ uptake remains regulated by TRPC3. [Ca²⁺]_mito changes in HeLa cells or HeLa-TRPC3 cells transfected with scrambled (sc) or indicated siRNAs in the absence or presence of 4 µM cyclosporine A (CsA) and evoked by 1.5 µM histamine in the presence of 300 µM Ca²⁺ (A), by 15 µM histamine in a Ca²⁺-free extracellular solution (B), or by 75 µM Ca²⁺ in digitonin-permeabilized HeLa cells (C). (A–C) (Right) Means ± SEM of peak [Ca²⁺]_mito changes normalized to that of sc HeLa of four independent experiments with the total number of HeLa and HeLa-TRPC3 cells, n = 103. **P < 0.01, ***P < 0.001 vs. sc HeLa. ^#P < 0.05, ^##P < 0.01. (D) Down-regulation of MCU by its RNAi-1 or -2 (i-1 or 2) in HEK 293 cells, in which MCU-myc was overexpressed. (E) [Ca²⁺]_mito changes in Trpc3^−/− MEF cells or Trpc3^−/− MEF-TRPC3 cells transfected with scramble (sc) or i-1, treated with 10 µM digitonin, and evoked by 300 µM Ca²⁺. (Right) Means ± SEM of peak [Ca²⁺]_mito changes normalized to that of sc of four independent experiments with the total number of Trpc3^−/− MEF and Trpc3^−/− MEF-TRPC3 cells, n = 69. ***P < 0.001, vs. sc Trpc3^−/− MEF. ^#P < 0.05, ^##P < 0.01.