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. 2021 Dec 1;9:765973. doi: 10.3389/fcell.2021.765973

FIGURE 3.

FIGURE 3

CypD inhibited or null liver mitochondria have reduced mitochondrial CRC and sensitized MPTP opening upon treatment of BH3 mimetics. (A) Representative traces of mitochondrial calcium uptake of WT liver mitochondria pre-treated with 2 µM cyclosporine A (CsA) and then with either 200 nM ABT-199 (red), 100 nM A-1331852 (orange), 10 nM S63845 (green), 100 nM ABT-737 (blue), 10 nM Obatoclax (purple), or with the vehicle control (black). Control WT liver mitochondria without CsA pretreatment is shown in grey. The blue arrow represents the addition of the BH3 mimetics. The black arrowheads represent the addition of 40 μM CaCl2. (B) Quantification of mitochondrial calcium retention capacity (CRC) calculated from mitochondrial calcium uptake traces, as in (A). (C) Representative trace of corresponding mitochondrial swelling to (A) of WT liver mitochondria pre-treated with CsA and then treated with BH3 mimetics and CaCl2. (D) Representative traces of mitochondrial calcium uptake of ppif −/− liver mitochondria treated with either 200 nM ABT-199 (red), 100 nM A-1331852 (orange), 10 nM S63845 (green), 100 nM ABT-737 (blue), 10 nM Obatoclax (purple), or with the vehicle control (black). The blue arrow represents the addition of the BH3 mimetics. The black arrowheads represent the addition of 40 μM CaCl2. (E) Quantification of mitochondrial calcium retention capacity (CRC) calculated from mitochondrial calcium uptake traces, as in (D). (F) Representative trace of the corresponding mitochondrial swelling to (D) of ppif −/− liver mitochondria treated with BH3 mimetics and CaCl2. Three independent experiments (n = 3) were performed for every panel. *p ≤ 0.05 for comparison the Veh. # p ≤ 0.05 for comparison the Veh w/CsA.