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. 2022 Aug 12;131(6):528–541. doi: 10.1161/CIRCRESAHA.121.320717

Figure 4.

Figure 4.

Inhibition of MCT1 (monocarboxylate transporter 1) prevents the enhanced uptake of malonate at lowered pH. A, Malonate uptake (5 mmol/L disodium malonate [DSM], 15 min) in C2C12 cells in the presence of lactate (0, 10 or 50 mmol/L). B, Lactate levels in C2C12 cells after 15 min treatment with varying concentrations of MCT1 inhibitors. C and D, Effect of MCT1 inhibition by AR-C141990 or AZD3965 on malonate (5 mmol/L DSM, 15 min) uptake (C) at pH 6 and subsequent succinate levels (D). E, C2C12 cells were incubated with DSM (5 mmol/L) for 15 min at various pH±10 µmol/L AR-C141990. F, MCT1 inhibition by AR-C141990 on malonate (5 mmol/L DSM, 15 min) uptake at pH 7.4 (A to F, mean±SEM, n=3 biological replicates, statistics: (A) Kruskal-Wallis with Dunn post hoc test). G and H, Effect of malonate (5 mmol/L DSM) on cellular oxygen consumption at pH 7.4 (G) or 6 (H) ±MCT1 inhibitor (10 µmol/L AR-C141990; data presented as nonmitochondrial respiration normalized mean oxygen consumption rate (OCR)±SEM of 3 biological replicates (n=12–16 technical replicates per biological replicate), statistics: Kruskal-Wallis with Dunn post hoc test). ATP indicates OCR in the presence of 1.5 µmol/L oligomycin; BL, baseline OCR; MAX, OCR in the presence of 1 µmol/L FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone); and NM, OCR in the presence of 4 µg/mL rotenone and 10 µmol/L antimycin A.