Figure 4.

PPi rescues the mitochondrial dysfunction of TNNT2 mutant induced pluripotent stem cell-cardiomyocytes. (A) Effect of PPi on mitochondrial function in TNNT2 mutant and isogenic control induced pluripotent stem cell-cardiomyocytes. Mitochondrial function was measured by extracellular flux analysis. OCR, cellular oxygen consumption rate. (B and C) Quantitation of mitochondrial functional parameters from (A). Mean ± standard deviation, n = 14–16 replicates per line, three independent differentiation batches. (D) Schematic showing expected labelling of carbon flow from glucose to tricarboxylic acid cycle intermediates when labelled with [¹³C₆]-glucose. (E–G) Abundance of [¹³C₆]-glucose-derived α-ketoglutarate, succinate, and citrate in TNNT2^HET induced pluripotent stem cell-cardiomyocytes cultured in the presence of [¹³C₆]-glucose with vehicle control (Ctrl) or PPi. Vehicle control-treated TNNT2^CORR induced pluripotent stem cell-cardiomyocytes is also shown for comparison. Data represent mean ± standard deviation, n = 9–18 replicates per condition, two independent labelling experiments.